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Stress, Immune Regulation, and Immunity: Applications for Asthma
Abstract
The neuroendocrine mediators reach the cells of the immune system either through the peripheral circulation or through direct innervation of lymphoid organs. Primary and secondary lymphoid organs are innervated by sympathetic nerve fibers. Lymphocytes and monocytes express receptors for several stress hormones, including CRH, ACTH, cortisol, norepinephrine, and epinephrine. Therefore, it is reasonable to conclude that the neuroendocrine hormones released during a stressful event could alter immune function and subsequently alter the course of immune-based diseases. The impact of psychological stress on immune function has been the subject of extensive research efforts. Using a variety of models from largely healthy humans undergoing various forms of natural and experimental stress models, stress has been associated with suppression of NK activity, mitogen- and antigen-induced lymphocyte proliferation and in vitro production of IL-2 and IFN-gamma. Psychological stress is also associated with a higher rate of in vivo hypoergy to common recall-delayed type hypersensitivity antigens. These studies have suggested that psychological stress suppresses various components of CMI responses. Also, data suggest that chronic stress does not simply suppress the immune system, but induces a shift in the type-1/type-2 cytokine balance toward a predominant type-2 cytokine response. Such a change would favor the inflammatory milieu characteristic of asthma and allergic diseases. Recent studies using well-controlled teenage asthmatic subjects demonstrated immunological changes (decreased NK cell cytotoxicity and cytokine alterations) in response to exam stress. These immune alterations are consistent with a cytokine milieu that could potentially worsen asthma. However, there were no changes in peak flow rates, self-report asthma symptoms, or medication use. The lack of correlation between stress and asthma symptoms may have been related to the timing of the visits in relation to the stressor, the duration of the stressor, disease severity, or a lack of accurate self-report data. Alternatively, stress-mediated exacerbations of asthma may require multiple alterations by stress, including cytokine dysregulation or vagal-mediated airway hyperresponsiveness. The rationale for stress management in asthma is based upon the notion that stress causes a change in immune balance that would favor asthma activity in susceptible individuals. This immune imbalance can be found in TH1/TH2 cytokine changes that occur with stress. Although it has not yet been demonstrated that stress can cause or directly influence the development of asthma, it is interesting to note that both the incidence and prevalence of asthma continue to increase and are higher in urban than in rural areas. Among other differences is the well-appreciated higher chronic stress levels associated with urban living.
... The Journal of Immunology, 2009, 182: 7888 -7896. P sychological stress can modulate immune and inflammatory cell function through neural and hormonal pathways that link the autonomic nervous and the immune systems (1)(2)(3)(4)(5)(6)(7)(8)(9). Physical and psychological stressors were shown to activate the hypothalamic-pituitary-adrenal axis and increase levels of circulating glucocorticoid hormones. ...
... Stress-induced increase in corticosteroid plasma levels, for example, inhibits the IL-12/ IFN-␥ regulatory axis, eliciting an immune-suppressed state. Interestingly, despite the increased circulating corticosteroid and catecholamine levels, chronic psychosocial stress has been long considered a major cause of exacerbation of allergic airway in-flammation (1,2,5,7,8,(13)(14)(15)(16). Experimental studies showed that asthma patients have increased bronchoconstriction after distressful experiences (3), listening to stressful interactions (17), or exposure to asthma-related visual brain stimulation (13). ...
... Although stress may impair asthma control (1,2,5,7,8,(13)(14)(15)(16), little evidence suggests that stress directly modulates immune function in the disease. In this study, we describe a unique murine model in which social stress and allergen exposure provides a platform to investigate the psycho-endocrine-immunological axis that regulates airway inflammation. ...
... The sympathetic nervous system and the hypothalamicpituitary-adrenal axis are the major pathway connecting the CNS and the immune system (reviewed in Elenkov et al., 2000). Several excellent reviews discuss in detail the origin, distribution, signaling and targets of sympathetic nerves in lymphoid organs (Felten et al., 1985;Felten and Felten, 1988;Felten, 1991;Straub, 2004), the effect of age (Bellinger et al., 1992;Madden et al., 1995Madden et al., , 1997Madden et al., , 1998Friedman and Irwin, 1997) and stress (Irwin, 1994;Marshall and Agarwal, 2000;Nagatomi et al., 2000;Sloan et al., 2008) as well as the relevance of dysregulated sympathetic nerovus system in immune-mediated disease (Bellinger et al., 1992(Bellinger et al., , 2008Madden et al., 1995;Friedman and Irwin, 1997;Marshall and Agarwal, 2000;Frohman et al., 2001;Straub et al., 2006;Wrona, 2006;del Rey and Besedovsky, 2008;Benarroch, 2009). ...
... The sympathetic nervous system and the hypothalamicpituitary-adrenal axis are the major pathway connecting the CNS and the immune system (reviewed in Elenkov et al., 2000). Several excellent reviews discuss in detail the origin, distribution, signaling and targets of sympathetic nerves in lymphoid organs (Felten et al., 1985;Felten and Felten, 1988;Felten, 1991;Straub, 2004), the effect of age (Bellinger et al., 1992;Madden et al., 1995Madden et al., , 1997Madden et al., , 1998Friedman and Irwin, 1997) and stress (Irwin, 1994;Marshall and Agarwal, 2000;Nagatomi et al., 2000;Sloan et al., 2008) as well as the relevance of dysregulated sympathetic nerovus system in immune-mediated disease (Bellinger et al., 1992(Bellinger et al., , 2008Madden et al., 1995;Friedman and Irwin, 1997;Marshall and Agarwal, 2000;Frohman et al., 2001;Straub et al., 2006;Wrona, 2006;del Rey and Besedovsky, 2008;Benarroch, 2009). ...
Innervation of the bone marrow (BM) has been described more than one century ago, however the first in vivo evidence that sympathoadrenergic fibers have a role in hematopoiesis dates back to less than 25 years ago. Evidence has since increased showing that adrenergic nerves in the BM release noradrenaline and possibly also dopamine, which act on adrenoceptors and dopaminergic receptors (DR) expressed on hematopoietic cells and affect cell survival, proliferation, migration and engraftment ability. Remarkably, dysregulation of adrenergic fibers to the BM is associated with hematopoietic disturbances and myeloproliferative disease. Several adrenergic and dopaminergic agents are already in clinical use for non-hematological indications and with a usually favorable risk-benefit profile, and are therefore potential candidates for non-conventional modulation of hematopoiesis.
... In contrast to acute stress, it has been shown that chronic stress produces deregulation of the immune response, both innate and adaptive [21,22], suppresses immunity by decreasing the number, transport and function of immune cells in peripheral blood [7], promotes proinflammatory activity driven by type 2 cytokines [23] and suppresses protective T cells, increasing the function of suppressor T cells in the skin [24]. It has also been observed that chronic stress suppresses immunoprotective parameters such as cell immunity driven by type 1 cytokines [25] and the number of monocytes and K lymphocytes in peripheral blood [26]. ...
... Apparently, these results are contradictory with respect to the immunosuppressive effects that chronic stress has on the immune response, innate as well as adaptive [7,[21][22][23][24][25]. However, other factors that can influence the direction (improvement vs. suppression) of the effects of stress or stress hormones and the nature of the immune response affected (immunoprotective, immunoregulatory/inhibitory or immunopathological) must be considered [4]. ...
Morpho-quantitative studies of the spleen indicate that the proportions of the compartments and subcompartments are stable in normal conditions. However, disorders due to stress can influence the number and function of the immune cells in this organ. The aim of this study was to determine, through the model of altering the early mother-infant bond and altering the late social bond through isolation, the effect on the morpho-quantitative characteristics of the spleen in adult Sprague-Dawley rats subjected to intermittent chronic stress in adulthood. Twenty-five newborn female rats were used, kept under the standardized lactation and feeding conditions. The rats were assigned randomly to 2 control groups (C1 and C2) and 3 experimental groups, exposed to early (E1), late (E2) or early-late (E3) adverse experiences and then subjected to intermittent chronic stress in adulthood (C2, E1, E2 and E3). The spleen of each animal was isolated and its morphometric characteristics were determined: volume density (Vv) of the red pulp, white pulp, marginal zone, splenic lymph nodule, periarterial lymphatic sheath and germinal center; areal number density (Na), surface density (Sv), number density (Nv), diameter (D) and total number of splenic lymph nodules. The mass of each compartment was also determined. A one-way analysis of variance (ANOVA) and Scheffé’s post hoc test were used for the statistical analysis. The p values were considered significant when they were less than 0.05 (*) and very significant at less than 0.025 (**). There were significant differences in the Vv of the red pulp, white pulp and their sub-compartments between the control and experimental groups. The white pulp increased significantly (P = 0.000) in E1, E2 and E3 compared to C1 and C2. The average Na and D values of the splenic lymph nodules were also higher in the experimental groups. The ANOVA for the mass of the spleen and the red pulp revealed no differences between the groups. The mass of the white pulp and its subcompartments was greater in the experimental groups. A higher proportion of white pulp in the experimental groups could be associated with an increase in spleen immune activity, with alterations depending on certain cell subsets. The chronic stress produced morpho-quantitative changes in the rat spleen, and these depended on the animal’s history of stress, whether it had been previously stressed or not, with further exposure to stress in adulthood.
... Depression can activate the SNS, triggering epinephrine release and stimulating noradrenergic fibers in lymphoid tissues. Released catecholamines binding to lymphocytes may enhance humoral responses (39). Concurrently, adrenergic receptors may trigger mast cells to release histamines and activate eosinophils in the airways. ...
Objective
Although extensive research has explored the link between mental disorders and asthma, the characteristics and patterns of this association are still unclear. Our study aims to examine the genetic causal links between common mental disorders (specifically, anxiety and depression) and asthma.
Methods
We conducted genetic analyses including linkage disequilibrium score regression (LDSC) and bidirectional two-sample Mendelian randomization (MR) analyses, and utilized summary statistics from recent large-scale Genome-Wide Association Studies (GWASs) in European populations, covering sensation of anxiety or depression, anxiety sensation, depression sensation, anxiety disorders, major depression disorder (MDD), and asthma.
Results
LDSC revealed significant genetic correlations among sensation of anxiety or depression, MDD and asthma (P < 0.017), highlighting potential genetic correlation between anxiety disorders and asthma (P < 0.05 yet > 0.017). In bidirectional two-sample MR, inverse-variance weighted (IVW) analyses suggested that genetic liability to asthma was significantly associated with an increased risk of sensation of anxiety or depression (OR = 4.760, 95%CI: 1.645–13.777), and MDD (OR = 1.658, 95%CI: 1.477–1.860). Conversely, IVW analyses indicated that genetic liability to anxiety disorders was not associated with an increased risk of asthma (P > 0.01), nor was genetic liability to asthma associated with an increased risk of anxiety disorders (P > 0.01). Furthermore, no significant genetic causal relationships were observed for other studied traits. Multivariate MR, after adjusting for body mass index and alcohol consumption, further corroborated the independent causal effect of genetic predisposition to MDD on the risk of asthma (OR = 1.460, 95% CI: 1.285–1.660).
Conclusion
Our study establishes MDD as a predisposing factor for asthma. Meanwhile, anxiety disorders are not causal risk factors for asthma, nor is the reverse true. It is recommended to closely monitor asthma symptoms in patients with MDD.
... High stress levels in both children and parents predicted onset of wheeze and asthma morbidity (e.g., severity, subsequent attacks) in children [41][42][43][44][45]. Chronic stress increased allergic airway inflammation and hyperresponsiveness in mouse models [46][47][48][49][50][51] and in asthma patients [52,53]. Stress may also increase immune dysregulation through direct effects on the endocrine system and autonomic neuronal control [54][55][56]. Indeed, stress can affect neural efferent nerves that may directly interact with airway eosinophils and promote inflammation and airway hyperreactivity [57]. ...
Background:
Population growth and climate change have led to more frequent and larger wildfires, increasing the exposure of individuals to wildfire smoke. Notably, asthma exacerbations and allergic airway sensitization are prominent outcomes of such exposure.
Summary:
Key research questions relate to determining the precise impact on individuals with asthma, including the severity, duration, and long-term consequences of exacerbations. Identifying specific risk factors contributing to vulnerability, such as age, genetics, comorbidities, or environmental factors, is crucial. Additionally, reliable biomarkers for predicting severe exacerbations need exploration. Understanding the long-term health effects of repeated wildfire smoke exposures in individuals with asthma and addressing healthcare disparities are important research areas.
Key messages:
This review discusses the need for comprehensive research efforts to better grasp wildfire smoke-induced respiratory health, particularly in vulnerable populations such as farmworkers, firefighters, pregnant women, children, the elderly, and marginalized communities. Effective mitigation would require addressing the current limitations we face by supporting research aimed at a better understanding of wildfire smoke-induced airway disease.
... Such responses are characterised by activation of the hypothalamus-pituitary-adrenal axis leading to increased levels of adrenal hormones such as glucocorticoid, epinephrine, and norepinephrine (Pruet 2003). On one hand, the increase in the levels of these hormones leads to activation of neuroendocrine mediators, which can increase or decrease proin ammatory cytokines in the peripheral circulation resulting in increased or decreased concentrations of immune cells (Hoffman-Goetz and Pedersen 1994; Pulsford et al. 1994;Marshall 2000, Pruett 2003). On the other hand, corticosteroids, which levels are elevated at stress, inhibit macrophage and lymphocyte function, thereby suppressing immune responses (Black 1994). ...
Environmental pollution and habitat loss and are in uencing the health status of wild animals and increase the risk of zoonosis outbreaks. For example, the ongoing urbanisation leads to significant habitat changes and burden of anthropogenic stressors. Bats are a diverse mammalian order occurring in urban areas. In a pilot study, we investigated the general immunity status of two common bat species along urban-natural gradients. We used haematological parameters as cellular immunity indicators and intensity of light pollution as a proxy for urbanisation level (i.e. anthropogenic stress) at the sampling points. We found higher total white blood cell counts, lymphocytes and neutrophil proportions in Nyctalus noctula from suburban and urban habitats in comparison to those from natural ones. At the same time Eptesicus serotinus, a species commonly living in cities, had a lower neutrophil level and a trend towards lower neutrophil-to-lymphocyte ratio and intoxication index compared to N. noctula which only uses the suburban-urban area seasonally. Our study suggests that the cellular immunity in bats is altered by urban stressors, yet depends on species-species-specific tolerance. We call for more research in this area and, as precaution principle, conservation of habitats in urban areas in order to mitigate the negative impact of urban stressors on the health of wildlife.
... For asthma, stress does not simply suppress the immune system of asthmatic patients, but breaks the balance of the Th1/Th2 cytokines, thus making them shift to the Th2 type. 42 For depression, stress (especially early life events and lack of interpersonal interaction) could enhance the inflammatory response. The high comorbidity rate of asthma and depression highly would suggest that there could be some common pathogenesis between them. ...
Asthma has become a serious global public health issue affecting approximately 14% of children worldwide. Asthma patients often accompany various mental disorders, such as depression, anxiety, and panic attacks, which could aggravate asthma symptoms. It can be summarized that in addition to pathological cellular and molecular immune processes, asthma also has a neural phenotype. The first part of this review summarizes the prevalence and economic burden of asthma in recent years. Then, the neurophenotype of asthma is described in terms of brain structural changes, molecular expression, and prevalence. Our literature search shows that the frontal lobe plays an essential role in asthma-related neurophenotypes. Finally, we assume that an electroencephalogram signal could be one of the directions of asthma neurophenotype diagnosis.
... Thus, the insensitivity of serum IL-6 levels to stress, which was observed in the present study, may be associated with the anti-inflammatory action of IL-6. The exposure of Damin gilts to continuous stress during the fifth week might have caused them to adapt to the environment during the late lactation period via a compensatory increase of the levels of beneficial inflammatory cytokines (Chrousos, 2000;Marshall Jr. and Agarwal, 2000). However, during the fifth week of lactation, the ability of Large White gilts to adapt to environmental stress decreased, which might have led to a decline in the production of immunological factors. ...
ABSTRACT We evaluated the maternal behavior, physiology, and reproductive performance of both Damin (Min-pig × Large White) and Large White gilts to identify the advantages hybrid sows offer with regard to stress relieve and improvement of the welfare level of sows during late lactation. First-parity Damin gilts (n = 40) and first-parity Large White gilts (n = 40) were farrowed in individual pens. Video surveillance was used to monitor the occurrence of lateral recumbency and compare it to other postures, such as ventral recumbency, defecation, urination, tail posture, sham-chewing, and bar-biting behaviors. Monitoring was conducted from 07:00 to 09:00 h and from 13:00 to 15:00 h on days 3 and 6 of each week from the third to the fifth week post-parturition. In addition, the concentrations of tumor necrosis factor-α, interleukin-6, and salivary α-amylase were assessed. During the fourth week postpartum, Damin gilts showed a higher frequency of postural changes from lateral recumbency to other postures and less ventral recumbency, sham-chewing, and bar-biting behavior compared with Large White gilts. However, no significant differences were found between Damin and Large White gilts with regard to urination, defecation, tail wagging, and “tail low” behaviors. The concentrations of serum interleukin-6, salivary α-amylase, and serum tumor necrosis factor-α were higher in Damin gilts than in Large White gilts during the fifth week postpartum. Damin gilts partly achieve lower stress levels during late lactation and better animal welfare than purebred Large White gilts.
... The following additional physiological findings contribute to the understanding of the role of the nervous system in immune disorders: i) According to Marshall and Agarwal receptors for several stress hormones including corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol, norepinephrine, and epinephrine are found on lymphocytes and monocytes [60]. ii) Research conducted by Marshall, Agarwal, Lloyd, Cohen, Henninger and Morris [61], demonstrated an increased frequency of viral infections, allergic or asthmatic reaction during examination stress in healthy medical students. ...
Despite the prevalence of autoimmune diseases, and the variety of proposed factors involved in their aetiology, the exact cause of autoimmune disorders is still unknown [1]. As psychotherapist specializing in work with parents for the last sixteen years, and a physician who has worked with adolescents for seventeen years, in this presentation, we propose to consider the analogy between the dynamics of the overprotective family and those of the overactive immune system in autoimmune disorders, and that they are both manifestations of the structures and mechanisms of narcissistic anxiety.
The overprotective parenting style is characterised by parents who present guarding behaviour that is excessive considering the child’s developmental stage and the actual risk level in their environment. Overprotective parents tend to obsess over their children’s physical and emotional safety, at a level that exceeds the actual level of risk [2]. The impact of overprotective family dynamics upon the emotional development of a child has been extensively discussed [3]. Analogous to this, autoimmune diseases are clinical manifestations of aberrant and "hyper-reactive" autoimmune responses to self-antigens of normal bodily constituents leading to inflammation, cell injury, or a functional disturbance [1]. Medical literature has suggested the correlation between emotional disorders and a variety of autoimmune diseases [4].
This presentation suggests to consider the possibility that high levels of anxiety underlie both overprotective manifestations. Instead of functioning as defence mechanisms aimed to protect the self, they are diverted into a direct attack on it.
... The following additional physiological findings contribute to the understanding of the role of the nervous system in immune disorders: i) According to Marshall and Agarwal receptors for several stress hormones including corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol, norepinephrine, and epinephrine are found on lymphocytes and monocytes [60]. ii) Research conducted by Marshall, Agarwal, Lloyd, Cohen, Henninger and Morris [61], demonstrated an increased frequency of viral infections, allergic or asthmatic reaction during examination stress in healthy medical students. ...
Despite the prevalence of autoimmune diseases, and the variety of proposed factors involved in their aetiology, the exact cause of autoimmune disorders is still unknown [1]. As psychotherapist specializing in work with parents for the last sixteen years, and a physician who has worked with adolescents for seventeen years, in this presentation, we propose to consider the analogy between the dynamics of the overprotective family and those of the overactive immune system in autoimmune disorders, and that they are both manifestations of the structures and mechanisms of narcissistic anxiety. The overprotective parenting style is characterised by parents who present guarding behaviour that is excessive considering the child's developmental stage and the actual risk level in their environment. Overprotective parents tend to obsess over their children's physical and emotional safety, at a level that exceeds the actual level of risk [2]. The impact of overprotective family dynamics upon the emotional development of a child has been extensively discussed [3]. Analogous to this, autoimmune diseases are clinical manifestations of aberrant and "hyper-reactive" autoimmune responses to self-antigens of normal bodily constituents leading to inflammation, cell injury, or a functional disturbance [1]. Medical literature has suggested the correlation between emotional disorders and a variety of autoimmune diseases [4]. This presentation suggests to consider the possibility that high levels of anxiety underlie both overprotective manifestations. Instead of functioning as defence mechanisms aimed to protect the self, they are diverted into a direct attack on it.
... Although some of the studies failed to confirm the efficacy of acupuncture for AR (2)(3)(4) , many studies reported positive results (5)(6)(7)(8)(9) in recent years and a systematic review concluded that acupuncture might be safe and effective treatment for AR (10) . Clinical practice guideline in AR from the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) also recommended acupuncture for AR patients who are interested in nonpharmacologic therapy (11) . ...
Background: Acupuncture can effectively alleviate the nasal symptoms of allergic rhinitis (AR); however, the mechanism is unclear. Previous studies suggested it may be related to improve hypothalamus-pituitary-adrenal (HPA) axis dysfunction.
Materials and Methods: The study was a randomised controlled trial including ninety patients with moderate to severe persistent AR. Subjects were randomised 1:1:1 to the 8-weeks treatment with mind-regulating acupuncture combined with intranasal glucocorticosteroids (INGC), conventional acupuncture combined with INGC and INGC alone (MA, CA, GC respectively). The primary outcome was the change from baseline in the Visual Analogue Scale (VAS) score of nasal symptoms. Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score was a key secondary outcome. The levels of corticotrophin releasing hormone (CRH), cortisol (COR) and adrenocorticotropic hormone (ACTH) were also analysed.
Results: MA, CA and GC reduced VAS score and total RQLQ by a similar degree, but the sleep domain of RQLQ significantly impro�ved in MA and CA compared to GC. Meanwhile, the COR and ACTH level increased, and CRH level decreased after treatment in MA and CA, but the changes showed no difference among the three groups after Bonferroni correction.
Conclusions: Although acupuncture combined with INGC may have potential effect on sleep quality, the combination therapy cannot further improve nasal symptoms or RQLQ compared to INGC alone in AR patients. The influence of acupuncture on HPA
axis needs to be further explored.
... In the cognitive-behavioral approach, the individual is helped to identify and correct misconceptions about him, the world and the future, and as a result prevent negative emotions and behaviors. According to the mind and body model in people with diabetes, cognitive impairment and negative automatic thoughts in diabetic patients are responsible for the occurrence of disease complications and immunological changes (16). The effect of cognitive-behavioral therapy (CBT) on improving the quality of life and reducing the stress and blood glucose levels in T2DM women has been effective (17,18). ...
Objective: The purpose of this study was to compare the effectiveness of compassion focused (CFT) and acceptance commitment (ACT) combined therapy with cognitive-behavioral therapy (CBT), on psychological well-being in women with type 2 diabetes (T2DM).
Materials and Methods: This is quasi-experimental. This study consists of three groups (two experimental and one control groups) and three stages (pre-test, post-test, and follow up). The statistical population was all T2DM women of Shahid Shabani Diabetes Center in Isfahan, Iran in 2017. The studied sample was 47 patients who were randomly distributed in three groups. The experimental group received a combination of the package of ACT and CFT for ten weekly two-hour sessions, the CBT group received ten weekly two-hour sessions of therapeutic intervention and the control group did not receive any therapeutic interventions. Data were analyzed by analysis of variance with repeated measurements using SPSS-24 software.
Results: The results showed that the scores of experimental groups participants in the post test of compassion therapy-ACT and CBT improved significantly compared to the control group in self-acceptance, positive relationships with others, purposeful life, individual development, environmental dominance and autonomy subscales (P-value= 0.001) .There exist a significant difference between the experimental group of compassion focused- ACT combined therapy and CBT in self-acceptance, positive relationships with others, purposeful life and individual -development subscales (P-value< 0.001).
Conclusion: Based on the findings, the combination therapy of compassion focused – ACT and CBT can be used to promote psychological well-being in diabetic patients.
... Increasing evidence indicates that psychological stress contributes to pathologic processes in various tissues. 1,2 Stress worsens not only atopic diseases (Table 1), including allergies, 3,4 anaphylaxis, 5 asthma, [6][7][8] and skin disorders, 9 especially atopic dermatitis (AD), 10 but also inflammatory and autoimmune diseases, 11 such as multiple sclerosis. 12 Stress is the most common trigger of mastocytosis 13 and mast cell (MC) activation syndrome, 14 which are characterized by increased number of MCs 15 or their reactivity, 16,17 respectively. ...
Objective
Atopic diseases worsen with psychological stress, but how stress contributes to their pathogenesis is still not clear. We review the evidence supporting the premise that stress contributes to allergic and inflammatory processes via stimulation of mast cells (MC) by neuroimmune stimuli.
Data Sources
Pubmed was searched between 1950-2019 using the terms allergies, atopic diseases, corticotropin-releasing hormone, inflammation, hypothalamic-pituitary-adrenal axis, mast cells, mastocytosis, neuropeptides, psychological stress, neurotensin, substance P.
Study Selections
Only papers published in English were selected based on their relevance to stress and mast cells, especially those that discussed potential mechanisms of action.
Results
Psychological stress worsens many diseases, especially asthma and atopic dermatitis (AD) and mastocytosis. This effect is mediated via MC stimulated by neuropeptides, especially corticotropin-releasing hormone (CRH), neurotensin (NT) and substance (SP), a process augmented by IL-33.
Conclusion
Understanding how stress stimulates MC to release pro-inflammatory mediators is important in advancing treatments for diseases that worsen with stress.
... Chronic psychological stress is believed to be a contributing factor in a number of illnesses and medical conditions including hypertension, cardiovascular disease (Williams, 1997), diabetes (Wales, 1995), obesity (Epel et al., 2000), asthma (Marshall & Agarwal, 2000), and cancer (Kiecolt-Glaser & Glaser, 1999). Further, stress has been found to cause immunosuppression (Kiecolt-Glaser, McGuire, Robles, & Glaser, 2002), and increased susceptibility to infectious diseases. ...
It seems that nearly every day a new study is published that links psychological stress to poor health outcomes. Psychological stress has been found to cause immunosuppression, increased susceptibility to infectious diseases, delayed wound healing, and to contribute to the development of psychological disorders. Yet, the implications of psychological stress as it relates to health disparities are seldom addressed. Chronic stress is an important but understudied factor that interacts with culture, socioeconomic status, and other psychosocial factors to act not only directly on physiological systems, but also to shape and influence health-related behavior. Research indicates that psychological stress acts through multiple pathways to influence health. Likewise, psychological stress and its impact on vulnerable populations may be addressed and managed at multiple levels. We define stress, and briefly review the literature on psychological stress in health disparities. We briefly describe several models of how stress negatively impacts health generally, and the pathways through which is believed to impact the health of some vulnerable populations specifically. We suggest ways in which policymakers, health systems, organizations, communities, and individuals can begin to work to reduce psychological stress and stress-related health inequities.
... In this approach, the patient is helped to identify and refine the false beliefs about him, the world and the future to prevent the creation of negative emotions and behaviors. Based on the mind-body model in diabetic patients, cognitive distortions and negative automatic thoughts in diabetic patients are responsible for the development of disease complications and immunological changes (15,16). Also, a study showed that CBT was effective in improving the quality of life and reducing stress and blood sugar level in type II diabetic women (17). ...
Objective: Diabetes is chronic and debilitating disease that affects
all aspects of a person's life. The purpose of this study was to
compare the effectiveness of compassion focused (CFT)-acceptance
commitment (ACT) combined therapy with cognitive-behavioral
therapy (CBT), on interpersonal forgiveness in women with type II
diabetes.
Materials and Methods: This was of quasi- experimental study
on three groups (CFT-ACT combined therapy, a cognitivebehavioral
and a control group) and three stages (pre-test, post- test
and follow up). Among diabetic women population, 47 patients were
selected purposefully and randomly assigned to three groups. Tow
experimental groups (CFT- ACT & CBT) received 120 minutes’
sessions of CFT- ACT and CB for10 weeks. The control group did
not receive any treatment .Data were analyzed by repeated measures
analysis of variance using SPSS-24 software.
Results: The results showed that the scores of experimental group
participants in the post test of CFT-ACT and CBT improved
significantly compared to the control group in all three components
of forgiveness, including reconnection and revenge control,
resentment control and realistic understanding (P-value: 0/000). The
experimental group of the combined therapeutic model was more
effective than the CBT group in the two components of resentment control and realistic understanding.
Conclusion: Based on the findings, the combination therapy of
CFT- ACT and CBT can be used to promote reconnection and
revenge control, resentment control and realistic understanding in
diabetic patients.
Keywords: Compassion-focused therapy, Acceptance and
Commitment therapy, Cognitive Behavioral Therapy
... In this approach, the patient is helped to identify and refine the false beliefs about him, the world and the future to prevent the creation of negative emotions and behaviors. Based on the mind-body model in diabetic patients, cognitive distortions and negative automatic thoughts in diabetic patients are responsible for the development of disease complications and immunological changes (15,16). Also, a study showed that CBT was effective in improving the quality of life and reducing stress and blood sugar level in type II diabetic women (17). ...
Objective: Diabetes is chronic and debilitating disease that affects
all aspects of a person's life. The purpose of this study was to
compare the effectiveness of compassion focused (CFT)-acceptance
commitment (ACT) combined therapy with cognitive-behavioral
therapy (CBT), on interpersonal forgiveness in women with type II
diabetes.
Materials and Methods: This was of quasi- experimental study
on three groups (CFT-ACT combined therapy, a cognitivebehavioral
and a control group) and three stages (pre-test, post- test
and follow up). Among diabetic women population, 47 patients were
selected purposefully and randomly assigned to three groups. Tow
experimental groups (CFT- ACT & CBT) received 120 minutes’
sessions of CFT- ACT and CB for10 weeks. The control group did
not receive any treatment .Data were analyzed by repeated measures
analysis of variance using SPSS-24 software.
Results: The results showed that the scores of experimental group
participants in the post test of CFT-ACT and CBT improved
significantly compared to the control group in all three components
of forgiveness, including reconnection and revenge control,
resentment control and realistic understanding (P-value: 0/000). The experimental group of the combined therapeutic model was more
effective than the CBT group in the two components of resentment
control and realistic understanding.
Conclusion: Based on the findings, the combination therapy of
CFT- ACT and CBT can be used to promote reconnection and
revenge control, resentment control and realistic understanding in
diabetic patients.
Keywords: Compassion-focused therapy, Acceptance and
Commitment therapy, Cognitive Behavioral Therapy
... By stimulating the body's "selfregulation system", acupuncture enables the body to reach a dynamic balance and integration. Current research proves that the NEI system plays an important role in the pathological mechanisms of allergic diseases [9]. The NEI system of patients undergoes significant change under stress conditions. ...
Background:
Patients with moderate and severe persistent allergic rhinitis (AR) have long-term physical and mental stress, leading to dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis, which results in recurrence of AR. Previous research has proved acupuncture can regulate the function of the neuron-endocrine-immune system and contribute to improving the quality of life of patients with AR. This research aims to investigate the mechanism of acupuncture on the HPA axis in patients with moderate or severe persistent AR.
Methods/design:
This randomized controlled trial aims to study the impact of acupuncture on the HPA axis of patients with moderate and severe AR. This research also aims to compare the curative effects of different treatments in three groups of patients: those receiving western medicine, western medicine and conventional acupuncture, or western medicine and mind-regulating acupuncture. We will study the therapeutic effect of acupuncture and the correlation between the changes of therapeutic indexes and experimental indexes after the treatments. Therapeutic indexes include the Visual Analog Scale (VAS) of nasal symptoms and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) for AR patients; experimental indexes include corticotropin releasing hormone (CRH), adreno-corticotropic hormone (ACTH), cortisol (CORT), interleukin 4 (IL-4), and interferon-γ (IFN-γ).
Discussion:
The results of this trial will provide evidence for the influence of chronic, long-term, repeated stimulation in patients with moderate and severe persistent AR and the impact of acupuncture on the HPA axis of these patients.
Trial registration:
Acupuncture-Moxibustion Clinical Trial Registry, AMCTR-IOR-16000009 . Registered on 22 August 2016.
... These hormones released during stress modulate leukocyte trafficking/decrease and result in the redistribution of leukocytes between the blood and other immune compartments [34] thus causing a drop in free circulating leukocytes. Therefore, physiological response to stressful events could alter immune function [35] which explains the significant decrease of mean lymphocytes and monocytes percentages in this study. The drop in leukocyte count has been reported also by Kotepui et al. [36] as opposed to other studies which reported an increase [37]. ...
Objectives: This study aimed at evaluating the effect of examination stress on the cardiovascular parameters amongst undergraduate students of the University of Buea, out of examination period (OEP) and during examination period (DEP). Experimental Design: This was a cross-sectional study. Place and Duration of the Study: The study was carried out at the University of Buea (Cameroon). The field and laboratory work was carried out from January to June 2016 within which are two examination periods and two weeks of first semester break. Methodology: A structured questionnaire was used to document student’s demographic information and number of hours slept. Blood pressure and heart rate were measured using automatic arm sphygmomanometer. Blood samples were collected for full blood count analysis using a haematology analyser. Stress was measured using Cohen Perceived stress scale (PSS) while salivary alpha amylase (sAA) concentrations were measured by ELISA. Data was collected and analysed from 772 (OEP=378 and DEP= 394) participants. Mann-Witney U-test and students T- test were used for statistical analyses. The significance level was set at P<0.05. Results: The prevalence of stress was 98.2% (387) DEP vs 97.4% (368) OEP (P=0.372) with PSS of (23.41±4.88 vs. 22.31± 4.53, P=0.002). The sAA concentrations was higher DEP (24.659 ± 16.384) than OEP (18.789±5.865) (P< 0.001). Among the haemodynamic and haematological parameters, SBP and HR were significantly higher DEP than OEP. There was a positive correlation between HR and sAA within both periods. WBC%, Lym%, Mon%, and MCHC were significantly lower (P<0.05) while Gran%, Plt and Pct increased DEP than OEP (P<0.05) with respect to stress. Conclusions: The prevalence of stress OEP vs DEP implies stress is an important problem in students. This is proven by the increase in PSS and sAA concentrations during examinations and can lead to impairment of cardiovascular parameters.
... GI secretion and motility are regulated not only by neurotransmitters and hormones, but also by neurons (12). In many instances chronic, sustained, unpredictable stress, whether physical or psychological, is the most deleterious, contributing to immune and endocrine dysfunction (22). The neuroendocrine hormones released during a stressful event could causes alterations in immune function and immune imbalance (23). ...
Background/aims:
Transient receptor potential ankyrin 1 (TRPA1) and substance P (SP), both expression in sensory neurons, have important roles in stress-induced duodenal lesions. The possible contribution of TRPA1 and SP to stress-induced duodenal lesions was explored by using the water immersion restraint stress (WIRS) rat model.
Materials and methods:
Western blotting, Real-time polymerase chain reaction (RT-PCR), and immunohistochemistry assay were used to evaluate the changes of TRPA1and SP expression in the dorsal root ganglia (DRG, T8-11), the corresponding segment of the spinal cord (T8-11), and the duodenum in a duodenal lesions rat model. The SP concentrations of duodenal mucosa were investigated using an enzyme-linked immunosorbent assay (ELISA). Duodenal lesions were assessed according to histopathological changes. TRPA1 specific antagonist HC-030031 was intrathecally or intraperitoneally performed to suppress the expression of both TRPA1 and SP for evaluating the roles of TRPA1 and SP in duodenal lesions.
Results:
In contrast to the control group, TRPA1 and substance P in the DRG (T8-11) and duodenum were up-regulated, and concentrations of SP in the duodenal mucosa were increased after WIRS (p<0.05), which are closely associated with duodenal lesions. SP concentrations in the duodenal mucosa were decreased and duodenal lesions were alleviated by pretreatment with TRPA1 antagonist HC-030031. We identified a protective role for HC-030031 in WIRS-induced duodenal lesions. Furthermore, we demonstrated that WIRS increased the concentrations of SP in the duodenal mucosa in a TRPA1-dependent manner. However, WIRS caused no significant changes of TRPA1 and SP in the spinal cord (T8-11) compared with the control group (p>0.05).
Conclusion:
Our study indicates that TRPA1 antagonist HC-030031 alleviates duodenal lesions. TRPA1 is activated and sensitized, therefore concomitant neuropeptide SP is released, which exerts a critical role in inducing and maintaining duodenal lesions following WIRS in rats. This provides evidence that neuroimmune interactions may control duodenal injury. TRPA1 may be a potential drug target to inhibit the development of duodenal lesions by stress-induced in patients.
... However, the association is largely confounded by psychological distress, which is central to the etiology of psychiatric disorders but can also give rise to allergies. Neuroendocrine hormones released in response to stressful events (e.g., traumas, chronic stressors) can suppress the immune system, alter immune function (i.e., dysregulating the type 2 cytokine response), and change the course of immune-based diseases [50]. One of our novel findings is that seasonal allergies were significantly associated with eating disorders. ...
Seasonal allergies have been associated with mental health problems, though the evidence is still emergent, particularly in the United States. We analyzed data from the National Comorbidity Survey Replication and the National Latino and Asian American Survey (years 2001–2003). Multivariable logistic regression models were used to examine the relations between lifetime allergies and lifetime psychiatric disorders (each disorder in a separate model), adjusting for socio-demographic variables (including region of residence) and tobacco use. Analyses were also stratified to test for effect modification by race and sex. A history of seasonal allergies was associated with greater odds of mood disorders, anxiety disorders, and eating disorders, but not alcohol or substance use disorders, after adjusting for socio-demographic characteristics and tobacco use. The associations between seasonal allergies and mood disorders, substance use disorders, and alcohol use disorders were particularly strong for Latino Americans. The association between seasonal allergies and eating disorders was stronger for men than women. Seasonal allergies are a risk factor for psychiatric disorders. Individuals complaining of seasonal allergies should be screened for early signs of mental health problems and referred to specialized services accordingly.
... In addition, the insensitivity of plasma IL-6 levels to stress was reduced, and this might be associated with the anti-inflammatory action of this cytokine. At the 5th week, Damin sows adapted better to the late lactation environment by increasing a compensatory and mediating immunoregulation with beneficial cytokine secretion [41,42]. However, the adaptability to the stress of late lactation of Large White sows decreased in the 5th week, and decreases in the levels of IL-6 were observed. ...
To improve the overall welfare levels of sows and to reduce stress levels at late 35-day lactation, we selected targeted behavioral indicators that might be associated with stress. Therefore, we monitored and evaluated the adaptive capability of two different breeds of sows to the farrowing environment. In this study, Damin sows (Large White × Min pig sows, n = 20) and Large White sows (n = 20) were farrowed in individual pens. Saliva was collected and tested for cortisol density at –15 min, and then at +15, 30, 60, 90, 120, 180 and 240 min after an adrenocorticotropic hormone (ACTH) stimulation test conducted at 20, 27 and 34 d post-partum. The postures, including ventral and lateral recumbency to other postures, defecating, urinating, sham-chewing and bar-biting behavior, were observed by video from 07:00 to 09:00 and from 13:00 to 15:00 on the 7th day of each week from the 3rd to the 5th week post-parturition. In addition, the concentrations of salivary interleukin (IL)-6, tumor necrosis factor (TNF)-α and secretory immunoglobulin (SIgA) were assayed after the observed behaviors. The results showed no significant difference between Damin sows and Large White sows in terms of behaviors at the 3rd week. Additionally, there were no significant differences between Damin and Large White sows in terms of the behaviors of ventral recumbency and bar-biting with the exception of lateral recumbency to other postures, sham-chewing, defecation and urination in the fifth week. Meanwhlie, there was significant difference between two breeds in term of ventral recumbency at the 4th week. The result of the ACTH test showed a significant difference between the Damin and Large White sows by the 27th and 34th days postpartum (P<0.01). In addition, the serological concentrations of IL-6 and TNF-α were not significantly different between the two breeds at the 3rd week postpartum. However, these indicators were significantly different at the 5th week postpartum (P = 0.000, and P = 0.003, respectively). The SIgA concentrations in saliva were significantly different between breeds at the 3rd week postpartum (P<0.01). In conclusion, both breeds of sows maybe in a state of stress after the 4th week postpartum. However, the Damin sows may be better than the Large White sows in terms of adapting to this farrowing environment.
... The main changes were down-regulation of Th1 (IFN-gamma and IL-2) and a selective up-regulation of Th2(IL-4, IL-5 and IL-6) cytokines (Kang et al., 2001). Skewed Th1/Th2 ratio and reduced NK cell numbers were detected in atopic rather than normal students in association with large exams indicating that atopics may be more strongly affected by stress than others (Höglund et al., 2006;Marshall et al., 2000). Reduction in NK cells was also detected in nursing students in response to academic exam whether healthy or asthmatic (Kang et al., 1988). ...
... It is known that the onset and exacerbation of asthma symptom often occur during times of increased psychological stress [33,34]. ...
Abstract Studies show that a significant proportion of young people suffering from childhood onset asthma later recovered, usually in adolescence. In this article we argue that an understanding of the differences between children who recover from asthma and those who do not would contribute to increased understanding of the pathogenic mechanisms of the disease and could provide new clues about prevention and treatment. We note that some researchers have recently published results from these kinds of investigations. This paper reports results regarding genetic determinants, distorted mechanisms of inflammation, and mind/body relationships. We also try to integrate findings from these 3 areas to formulate general conclusions about the pathogenesis of asthma.
... Increased levels of proinflammatory cytokines such as IFN-γ (T helper cell type 1 (Th1) cytokine) and a rapid but tissue-damaging cellular immune response constitute the immune system response [12]. Cortisol and catecholamines decrease the production of tumor necrosis factor-alpha (TNF-α) by antigen-presenting cells and promote Th2 responses via the release of interleukin (IL)10, IL13 and IL4 [13]. This process permits the immune system to halt acute responses but also favors allergic diseases [14,15]. ...
Psychoneuroimmunoendocrinology, which was first described in 1936, is the study of the interactions between the psyche, neural and endocrine functions and immune responses. The aim of psychoneuroimmunoendocrinology is to apply medical knowledge to the treatment of different allergic, immune, autoimmune, rheumatic, neoplastic, endocrine, cardiovascular and dental pathologies, among other disorders. Epigenetic factors and major stresses from different types of stimuli acting through distinct pathways and neurotransmitters are highly involved in altering the psychoneuroimmunoendocrine axis, resulting in the emergence of disease. The main purpose of this report is to expand the understanding of psychoneuroimmunoendocrinology and to demonstrate the importance of the above-mentioned interactions in the etiology of multiple pathologies. In this review, a search of the medical literature using PubMed (free access search engine for the Medline database of the National Library of Medicine of the United States) over the years 1936 to 2016 was conducted, and descriptive and experimental studies and reviews of the scientific literature were included.
... Isto tako, niz istraživanja jasno pokazuje povezanost između psihološkog stresa i bolesti vezanih uz funkciju imunosnog sustava, poput povećane podložnosti infekcijama dišnog sustava (Shephard i Shek, 1994), HIV-a (Leserman i sur., 2007), autoimunosnih bolesti kao što su multipla skleroza, dijabetes tipa I ili astma (Cox i Gonder-Frederick, 1992;Marshall i Agarwal, 2000;O`Leary, 1990). ...
In recent psychology literature very few plausible conceptions of the relations between personality and health outcomes have been proposed. It goes about four dominant theory models trying to explain the processes and mechanisms lying in the core of that complex relation. The models are based on the assumptions about the existence of physiological mechanisms (stress) in the background of relations between personality and health outcomes; about the existence of close links between personality and physical health derived from equivalent constitution predisposition; about the influence of the personality on health in which the risky/useful behaviour occurs as a mediator, respectively the active choice of the milieu or health risky situations; and about the existence of a connection between the personality and the so-called patient's behaviour as one of the health outcomes. Although the researchers obviously agree that there is not only one connection between the personality and an increased risk of falling sick, the multi dimensionality and multi directivity of such relations seems rather to be a rule, whereas the majority of researches in this field still try to check if a certain feature of personality is connected to a certain illness, a part of the illness development process or certain risky factors of that illness. That is to say that the existing draft researches are not set in the way they can detect a multiple connection or causality between tested variables, which results in the absence of an integral picture of the relations between personality and health outcomes. That is why the primary suggestion of this paper would be to direct the researchers to test the proposed models, as well as to try to integrate them into one broader model which needs to be tested. A better understanding of how and why the personality influences the health and the illness, namely who gets sick and why, would make it possible to develop more efficient illness prevention programmes and health promotion.
... Nowadays, there are a lot of theories to explain the mechanisms of airway hyperresponsiveness (AHR) such as immune imbalance [1], neurogenic inflammation [2], airway infection and inflammation [3] and epithelial defect [4] and these theories explain the mechanisms and pathologies of AHR respectively from different perspectives, but cannot explain all the manifestations of AHR. Now, most scholars accept the opinion that diseases with AHR such as chronic bronchitis, asthma and COPD are chronic airway inflammation [5]. ...
Background/Aims: The previous study in our lab showed that Nodal molecule on bronchial epithelial cells (BECs) was modulated by all kinds of lung microbes. The present study was designed to determine the effects of Nodal on proliferation of BECs and BECs-induced differentiation of T-helper (Th) cells. The epigenetic mechanisms of Nodal expression following treatments of different lung microbes were also identified. Methods: Real-time polymerization chain reaction (PCR) and western blot were used to determine the expression of Nodal. Flow cytometry was used to observe the effects of proliferation of BECs and subsequent BECs-induced differentiation of Th cells. Methylation levels of CpG islands in Nodal promoters were also analyzed by time of flight mass spectrometry. Results: The results showed that Nodal promoted proliferation of BECs and BECs-induced differentiation of Th cell from Th1 to Th2 and Th17. Nodal promoter showed a hyper-methylation in normal BECs. Through methylation modification in the promoter, P. aeruginosa or A.baumanni inhibited the expression of Nodal while RSV promoted the expression of Nodal. Conclusions: Our data showed that Nodal promoted Th2 and Th17 differentiation and inhibited Th1 differentiation which may cause imbalance of airway microenvironment. P. aeruginosa or A.baumanni may be hopeful for the treatment of airway hyperresponsveness by inhibition Nodal expression through DNA methylation modification in the promoter.
... Zaburzenia oddychania w przebiegu astmy oskrzelowej są jednym z fizjologicznych mechanizmów rozwoju obniżonego nastroju i lęku [9,12]. Należy podkreślić, że narażenie na przewlekły stres drogą mechanizmów psychoneuroimmunologicznych indukuje różnicowanie limfocytów w kierunku Th 2 [26][27][28]. Uwarunkowanie astmy oskrzelowej przez zachowanie i styl życia nasuwa pytania o udział czynników psychicznych w patogenezie i rozwoju tej choroby. Kolejnym zagadnieniem jest znaczenie korelacji zmiennych psychopatologicznych z obiektywnymi wynikami badań spirometrycznych i ciężkością astmy oskrzelowej [28]. ...
Introduction: Bronchial asthma is a serious health problem worldwide. The prevalence of asthma is still high and patients represent a wide range of age and socio-economic status. Despite progress in diagnostic and therapeutic options, several studies have shown that asthma has an impact on health-related quality of life, length of hospitalization, prognosis and patients' coping. Obturative disorders are associated with considerable emotional burden of the patient, which may result in the development of mood disturbances and anxiety disorders. Research more often than before emphasizes the clear role of psychopathological factors in the course of bronchial asthma. Aim: To assess the correlation between subjective and objective obstruction symptoms and the intensity of anxiety as a condition, and to estimate the intensity of anxiety and depression in patients suffering from bronchial asthma. Material and methods: The study enrolled 140 patients diagnosed with bronchial asthma and 100 healthy people, as a control group. Structured anamnesis was obtained and spirometry was performed in compliance with the standards set by the Polish Society of Lung Disease. Disturbances of ventilation and their severity were estimated according to the GINA Report. All the patients were assessed using the Beck Depression Inventory and the Spielberger State-Trait Anxiety Inventory (STAI). The subjective dyspnoea levels were estimated with the Borg scale. Results and conclusions: Multiple positive correlations were found between psychopathological factors and bronchial asthma patients versus the control group. Depression and dyspnoea modified the level of asthma severity according to GINA, grade of asthma control test and sensitivity to asthma treatment by ATS. A positive correlation was found between the declared dyspnoea level and the intensity of depression (p < 0.05) as well as the intensity of using inhaled and oral glucocorticosteroids (GCS) (p < 0.05) and inhaled short-acting beta agonist (SABA) and long-acting beta agonist (LABA) (p < 0.05). Anxiety-state, anxiety-trait and depression modified the feeling of dyspnoea (p < 0.001). Depression and dyspnoea determined pulmonary function test results (FEV1, FVC, FEV1%FVC). A positive correlation between psychopathological variables was observed in the study group of patients with bronchial asthma versus the control group.
Background:
Chronic respiratory disease disproportionately affects residents of Appalachia, particularly those residing in Central Appalachia. Asthma is particularly burdensome to Central Appalachian residents regarding cost and disability. Improving our understanding of how to mitigate these burdens requires understanding the factors influencing asthma control among individuals with asthma living in Central Appalachia, specifically rural Kentucky.
Methods:
This community-based, cross-sectional epidemiologic study used survey data to identify characteristics associated with uncontrolled and controlled asthma. The designation of "uncontrolled asthma" was based on a self-report of ≥ 2 asthma exacerbations in the past year. Individuals with ≤ 1 or no exacerbations were considered to have controlled asthma. Chi-square or Fisher exact tests assessed the association between categorical variables and asthma control categories. Logistic regression was conducted to determine the impact of factors on the likelihood of uncontrolled asthma.
Results:
In a sample of 211 individuals with self-reported asthma, 29% (n = 61, 46 females) had uncontrolled asthma. Predictors of uncontrolled asthma included depression (odds ratio 2.61, 95% CI 1.22-5.61, p = .014) and living in multi-unit housing (odds ratio 4.99, 95% CI 1.47-16.96, p = .010) when controlling for age, sex, financial status, and occupation. Being overweight or obese was not a predictor of uncontrolled asthma. Physical activity and BMI did not predict the likelihood of uncontrolled asthma.
Conclusion:
This study highlights significant challenges rural communities in Appalachian Kentucky face in managing asthma. Factors like depression, housing conditions, and a lack of self-management strategies play pivotal roles in asthma control in this population.
Levels in wastewater of human stress biomarkers, such as cortisone (E), cortisol (F), tetrahydrocortisone (THE), and tetrahydrocortisol (THF) may serve as indicators of population wellbeing and overall health. This study examined the stability of these biosignature compounds in wastewater to inform on their applicability for use in wastewater-based epidemiology (WBE). Wastewater from two undisclosed U.S. municipalities were fortified with the above four biomarkers of stress to a concentration of 10 ppb, and their decay was studied at three temperatures (15, 25, and 35 °C) over 24 h in oxic and anoxic conditions. Samples were analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS) in conjunction with the isotope dilution method for absolute quantitation. Results demonstrated short-term persistence (24 h) of biomarkers at low temperatures (15 °C), and accelerating kinetics of decay that were positively correlated with temperature increases. Among the four biomarkers evaluated, the tetrahydro derivatives were the most long-lived sewage-borne stress biomarkers and these are recommended therefore as prime analytical targets for use in WBE when tracking population stress. Statistical analyses using a non-parametric Wilcoxon test further revealed no significant differences (p > 0.05) between oxic and anoxic decay rates for all stress biomarkers in wastewater from all study locations, regardless of the prevailing temperature regime. This negative finding is worthy of reporting because it suggests the feasibility of straightforward modeling of stress hormone decay, irrespective of whether the sewerage system monitored contains fully filled, pressurized pipes or partially filled gravity flow pipes, whose filling level, and with it its redox conditions, are known to fluctuate over time with water use and storm events.
Like the lung, skin, and nose, the external eye is a common target of allergic inflammation. Ocular allergy (OA) represents a collection of underestimated diseases of the eye observed in children and adults. The ocular manifestations are the expression of multifactorial immune mechanisms that generally have a good prognosis, but for a few patients, long term inflammation may remarkably reduce the visual function. Evidence suggests that other co-participant systems, including epigenetic, genetic, environmental, individual factors, sex hormones, and the central and autonomic nervous systems may influence the ocular response from distant sites. This is consistent with the concept that the eye is an organ fully integrated with the rest of the body and that the therapeutic approach should be holistic, dynamic, and personalized. For instance, androgens and estrogens binding to receptors on the ocular surface and the continuous cross-talking of neuromediators and growth factors with immune cells act to maintain the ocular surface homeostasis in response to environmental challenges. The immune system links and regulates the response of the ocular surface. Complex and incompletely understood mechanisms influence the innate and adaptive immune responses and generate different OA phenotypes and endotypes discussed in the present review.
This study aimed to investigate the effect of a treadmill exercise on hematological and serum biochemical parameters and the expression of immune-related cytokine genes in leukocytes. For the experiment, six healthy adult dogs were divided into exercise and control groups. The exercise group performed an endurance exercise three times a week for four weeks. Blood samples were collected before exercise, two weeks after exercise, and post-exercise, and hematological and serum biochemical analysis and cytokine gene analysis were conducted. In the exercise group, white blood cell count (WBC), aspartate aminotransferase, serum alkaline phosphatase, and glucose levels were significantly decreased, but there was no change in the control group. The mRNA expression of TNF-α, IFN-γ, IL-1β, and IL-4 was significantly decreased in the exercise group compared to the control group. There was no difference in IL-6, IL-8, and IL-10 mRNA expression between groups. The results in the current study demonstrate that short-term moderate-intensity endurance exercise alters WBC levels and mRNA cytokine expression in leukocytes and may have a meaningful effect on immune health in dogs.
Introduction: Diabetes is a chronic disease that affects all aspects of a person›s life. The aim of this study
was to compare «Combined Therapy Package Focused on Compassion and Acceptance and Commitment
Therapy» with «Cognitive Behavioral Therapy» on depression and glycosylated hemoglobin in women with
type 2 diabetes.
Methods: The present study was performed in a quasi-experimental 3-group method with pre-test post-test
and 2-month follow-up. 47 women with type 2 diabetes referred to Shahid Asghar Shabani Diabetes Clinic
in Isfahan in 2017 were selected by purposive sampling. Then, by simple random assignment and using the
lottery method in 3 treatment groups, «Combined Therapy Package Focused on Compassion and Acceptance
and Commitment Therapy» with «Cognitive Behavioral Therapy» and control were replaced. Data were
collected using a demographic questionnaire, “Beck Depression Inventory” and Glycosylated Hemoglobin test
(HbA1C). Both groups received 10 sessions of 2 hours per week of treatment intervention. The control group
did not receive any treatment intervention. Data were analyzed in SPSS. 24.
Results: The scores of the participants in the post-test intervention groups «Combined Therapy Package
Focused on Compassion and Acceptance and Commitment Therapy» « and «Cognitive Behavioral Therapy»
had a significant decrease compared to the control group in depression (P<0.05). «Combined Therapy Package
Focused on Compassion and Acceptance and Commitment Therapy» was significantly higher than «Cognitive
Behavioral Therapy» on depression (P<0.05), but in the case of Glycosylated Hemoglobin, the results showed
that the scores of participants in the intervention groups there were no significant differences in the post-test
of «Combined Therapy Package Focused on Compassion and Acceptance and Commitment Therapy” and
«Cognitive Behavioral Therapy” (P> 0.05).
Conclusions: «Combined Therapy Package Focused on Compassion and Acceptance and Commitment
Therapy» and «Cognitive Behavioral Therapy» reduced depression in patients with diabetes. Therefore, the
use of this method to reduce depression in diabetic patients is suggested.
Keywords: Compassion Focused Therapy, Acceptance and Commitment Therapy, Cognitive Behavioral
Therapy, Diabetes, Depression, Glycosylated Hemoglobin.
Stress-related disorders are diverse and they may be mental and physical. Often, several body systems and organs are involved simultaneously. The pathophysiology of stress-related disorders involves many factors: an observable or perceived stressor, an individual dynamically evolving vulnerability and maladaptation leading to imbalance, as well as environmental, cultural, gender and life-cycle variables. There is a need to develop a comprehensive quantifiable stress assessment instrument. It would be based on the ‘stress factor’, a dimension that would integrate biological, psychological, social, economic and spiritual parameters and would allow for cultural sensitivity. It would contribute to clinical operational sophistication and would illuminate treatment options and multidimensional well-being interventions. Hopefully, it would facilitate development of culturally sensitive pharmaceutical or biophysiological adaptogens and homeostatic interventions.
Background:
In this study, we aimed to investigate the effects of aerobic exercise training on the serum IL-4/IFN-γ ratio (Th1/Th2 balance), testosterone/cortisol ratio, levels of cortisol, testosterone, estrogen, and progesterone, and body mass index (BMI) and to determine the relationship between changes in these variables in women with asthma.
Materials and methods:
Twenty-one women with mild to moderate asthma and regular menstrual cycles were selected in this study. Eleven women in the exercise group participated in the aerobic exercise program (60 min/day, three days a week in the evening). Peripheral blood samples were collected before (week 0) and after (week 12) the program. The samples were analyzed to determine the levels of sex hormones and cortisol via chemiluminescence assay, and cytokines were examined by ELISA assay.
Results:
The findings showed a significant increase in the Th1/Th2 ratio and a decrease in cortisol and BMI in the exercise group, compared to the control group (P<0.05). There was no significant correlation between changes in cortisol, sex hormones, and BMI and the increase in Th1/Th2 ratio.
Conclusion:
The present results suggested that moderate aerobic exercise enhances the Th1/Th2 ratio, independent of changes in steroid hormone level and BMI in women with asthma.
Introduction: When a person is in a state of anesthesia - sedation, the realization of the stress reaction is carried out through the mesocortical - limbic system, while performing intensive therapy outside sedation - through the amygdala and the hippocampus. In this regard, the response of the stress system under anesthesia and outside it will be different and, consequently, the evaluation of reactions during anesthesia is extremely interesting and necessary for targeted (individual) choice of combinations of drugs for anesthesia, depending on their effect on the links of the stress system. The more interesting is the response of the stress system in the conditions of the existing pathology, which in itself is accompanied by a stressful response.
Objectives: Evaluation of the reaction of the stress system (with the identification of age-specific features), determining the response characteristics of the stress-realizing and stress-limiting links, determining the total response of the stress system, depending on the combination of drugs used for general anesthesia on the clinical model of general surgical acute stress (adults and children).
Methods: Multicentre open clinical trial (2003-2015). This article presents the data of the group without the syndrome of intracranial hypertension (WSICH) - a general surgical group: 78 adults and 87 children. The group without SICH was interesting, as a group of "typical response" to stress in the form of trauma, emotional stress, pain factor. Two types of total intravenous anesthesia were used: standard (SA) - fentanyl, propofol and modified (MA) - fentanyl, propofol, ketamine, sodium oxybate. The markers of activity of the stress system (cortisol, corticotropic releasing factor (CTRF), β-endorphin, serotonin, histamine) were studied, the concentrations of interleukins in the blood serum (IL-4, IL-6, TNFa, IL-lß, IL-2). The study was conducted in the preoperative period and on the 5th-7th day after the operation. Statistical processing of the results was carried out.
Results and discussion: The normal initial reaction of the stress-realizing-link (SR) of the stress system was determined (the normal stress-typical stress response in adults and children) on preoperative (psycho-emotional) and pain (traumatic) stress, which is expressed in: normal level of cortisol (adrenal level); normal level of CTRF (hypothalamic level); increased level of histamine; The normal level of IL1; normal level of IL6; increased IL2; decrease in the level of TNFα. The normal initial reaction of the stress-limiting-link (SL) of the stress system is determined which is expressed in: normal serotonin level in children and increase in 30% of adults (a typical pathophysiological reaction associated with age, which demonstrates the "vulnerability" of the SL link in adults); Reduction of β-endorphin level (a discussion on the need to enhance opioid exposure in order to prevent inadequate anesthesia); An increase in IL4 mean values. The typical reaction of the SR and SL - stress system links to the surgical intervention (surgical stress) using standard (group SA) and modified (group MA) variants of TIA was revealed. For the SR-link, increased cortisol levels, increased CTRF level, normalization of histamine level, normalization of IL1 indices, a decrease in IL6 level, an increased level of IL2, an increase in the level of TNFα. For the SL-link, serotonin level was decreased (decrease of the SL potential and the need for additional activation via NMDA receptors), increased β-endorphin level (adequacy of opioid stimulation of the SL-link), an increase in IL4 in 75% of adults and 80% of children Need for additional stimulation via GABA receptors).
Conclusions: The "norm of pathology" (or "stress-norm") of the reaction of the SL-link (activation of stress-limitation), which can be estimated as normal when it is identical to the stimulation of the SR-link, for leveling the destabilizing influence of SR-stimulation, that is, Vegetative stabilization is achieved. In contrast to the SR-link, the possibility of combinations of drugs for general anesthesia to the activity of the SL-link receptors was revealed, the "point of application" for drugs was shown, with the prospect of developing techniques (new combinations) that could affect serotonin metabolism in the brain. It is possible to introduce a new concept - stress-limiting anesthesia, which is necessary, due to the received data that "depth of anesthesia" and "adequacy of anesthesia" are not identical concepts. Preparations for general anesthesia affect, first of all, the activity of the SL-link of the stress system and it is due to their combinations based on the initial activity of the stress system that it is possible to achieve adequate stress-limiting anesthesia.
Introduction: The global incidence and prevalence of allergic diseases are increasing as is the intensity and duration of excessive psychological stress due to multiple factors associated with living in today’s world such as personal, social and political unrest, increased fear and anxiety and/or depression often leading to hopelessness. Both allergy and chronic psychological stress are characterized by immune imbalances that have similar characteristics. Thus it is reasonable to posit that the two are interactive and that stress may induce as well as complicate at least some allergic diseases.
Areas covered: Stress management/reduction has been proposed with various physical, pharmacological and psychological interventions for both preventive and therapeutic reasons. A useful intervention involves mindfulness techniques which allow the individual to put their life situation in context for better personal management.
Expert commentary: Future studies must be developed that will further examine the role of excess psychological stress in specific allergic diseases and evaluate the effectiveness of various stress intervention protocols, particularly those involving mindfulness, to determine which individual would best respond clinically to which intervention. When this is accomplished, assessment and treatment of psychological stress will become a standard component of clinical care for allergy, asthma and other immune-based diseases.
Due to the rapid growth of the fetus it is particularly vulnerable to insults and changes in hormonal milieu. Therefore, is suggested that adverse situations experienced by the pregnant mother can alter the development and health of offspring, mainly due to the permeability of the placental barrier to various hormones and substances. The aim of the present investigation was to study the effects of prenatal stress in the regulation of pulmonary allergic inflammation, employing the murine model of experimental asthma. For this purpose, were used virgin female mice, Swiss lineage, of 50 days old. The models used were foot shock to induce prenatally stress, and "New York subway" stress to induce postnatally stress. Females were divided into 4 groups: CC group: not stressed females; CE group: postnatally stressed females (PND60); EC: females born from stressed mothers (GD15 to GD18); EE Group: females born from stressed mothers (GD15 to GD18) (footshock) and postnatally stressed (PND60). The induction of allergic pulmonary inflammation was done through sensitization of animals with 0,1 mg.Kg-1 sc of ovalbumin (OVA) solution, to further evaluate leukogram, bronchoalveolar lavage (BAL) hematopoietic marrow cellularity and neurochemistry. The experiments were performed 24 hours after the last session of nebulization. The number of BAL cells was significantly higher in EE group animals compared with the CC group (P
Exposure to chronic stress before and well after the induction of endometriosis is reported to increase lesion sizes in rats, but it is unclear whether stress, exposed shortly after the induction of endometriosis, would also promote the development of endometriosis, nor is it clear what the underlying possible molecular mechanism is. This study was undertaken to test the hypothesis that chronic stress can promote the development of endometriosis. A prospective randomized mouse experiment was conducted that subjected mice with induced endometriosis to predator stress. In addition, a cross-sectional immunohistochemistry study was performed in ectopic and eutopic endometrial tissue samples from age- and roughly menstrual phase-matched women with ovarian endometriomas. It was found that the chronic psychogenic stress induced epigenetic changes in the hippocampus in mouse independent of endometriosis. It was also found that chronic psychogenic stress induced epigenetic changes in the hippocampus of mice with endometriosis, and seemingly activated the adrenergic signalling in ectopic endometrium, resulting in increased angiogenesis and accelerated growth of endometriotic lesions. Thus, chronic psychogenic stress promotes endometriosis development, raising the possibility that the use of anti-depressants in cases of prolonged and intense stress might forestall the negative impact of stress on the development of endometriosis.
Asthma is a complex inflammatory disease of the airways and acupuncture is one of the effective therapies widely used to treat asthma in China. The aim of the study was to evaluate the regulatory role of acupuncture in airway inflammation and the hypothalamic-pituitary-adrenal (HPA) axis activity in OVA-induced murine asthma model. Our results demonstrated that acupuncture was effective in suppression of AHR, inhibition of total leukocyte, neutrophil, lymphocyte and eosinophil counts in BALF, attenuation of airway inflammation and TNF-α, IL-1β, IL-5 and eotaxin secretion. Furthermore, the HPA axis activity was also regulated by acupuncture, which included promotion of adrenocorticotropic hormone and cortisol secretion in the plasma. Our findings revealed that acupuncture could attenuate airway inflammation and regulate HPA axis and immunologic function in the OVA-induced murine asthma model, which may provide support to better understand the contribution of acupuncture to the regulation of airway inflammation and HPA axis activity in asthma.
Anxiety symptoms are common in chronically medically ill children and can have unique issues which make their management complex. Anxiety can precede the medical illness, be a consequence of the illness, or the two conditions may coexist with no clear chain of causality. As illustrative examples, certain medical conditions particularly notable for their relationship to anxiety are discussed in greater detail. These include asthma, headache, inflammatory bowel disease, other forms of gastrointestinal illness like irritable bowel syndrome, and cancer. For each of these conditions we discuss the impact of preexisting anxiety as well as how (psychologically and biologically) these illnesses can lead to anxiety. Psychotropic medication, psychotherapy, psychoeducation, family therapy, group therapy, and improved psychosocial supports are all options for management and have varying roles depending upon the particular medical and psychological concerns of a given patient. Addressing this anxiety is critical, as evidence has shown that increased levels of anxiety in the child and in their family can lower health-related quality of life, interfere with effective family functioning, and at times even biologically worsen the course of the illness itself.
Asthma, one of the most common chronic diseases in all socioeconomic groups in the United States, imposes a particularly heavy burden on residents of inner cities. The dimensions of this excess burden include asthma prevalence, morbidity, and mortality. 1-8 Inner city residence, low socioeconomic status (SES), and racial and ethnic minority group status are closely intertwined in the United States. This intermingling makes it difficult, if not impossible, to fully disentangle the independent relationship of each of these characteristics to asthma.
Background: Stress can be associated with an acute exacerbation of asthma symptoms. Methods: To explore mechanisms linking stress and asthma exacerbation, we used an animal model that combines an established allergic airway inflammation protocol with exposure to stress. Female CBA/J and BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and challenged with OVA-aerosol. Some mice were additionally exposed to sound stress for 24 hours. Results: In both strains we observed a significant increase of total cell count and eosinophil numbers in the BAL fluid of stressed animals. Immunohistochemistry on lung sections revealed an increase of gdTCR + T cells, a significant decrease of CD8 + T cells and apoptotic cell bodies in stressed and OVA-sensitized CBA/J mice. In the BALB/c strain, we observed significantly higher cell counts of Ki67 + proliferating cells after stress.
Recent basic and applied developments in the field of immunophysiology have deepened the insights into the mechanisms that are involved in neuroimmune interaction. The signal-receptor problem is being addressed intensively. The use of modern accurate and informative experimental techniques has made it possible to obtain data that provide solid evidence for neuroimmune interaction. Some of the problems are now being addressed by cutting-edge experimental techniques, including the use of DNA microarrays for studies at the genomic level. Current progress in the field of immunophysiology is characterized by intense studies of very diverse aspects of the problem, ranging from the molecular mechanisms of interactions between the neuroendocrine and immune systems to the clinical manifestations of neuroimmune disturbances. The search for therapeutic means to correct such disturbances is ongoing. The focus of scientific investigation shifted from analysis of the effects of excision of cervical sympathetic ganglia on immune function to studies of the effects of lesioning of hypothalamic structures. An obvious and logical further step in the development of immunophysiology was to study brain functions during the course of the development of the body's response to an antigen. A significant advance in NIB was achieved by detailed studies on the innervation of lymphoid organs, including not only their external neural input, but also the internal distribution of nerve fibers and endings within the organs of the immune system.
Noradrenaline and adrenaline belong to catecholamines, a family of chemical compounds containing a catechol or 3,4-dihydroxyphenyl group and an amine function. Together with dopamine, they are the most abundant and important catecholamines in the human body and are all produced fromtyrosine, a non-essential amino acid which is both obtained from dietary proteins or in turn synthesized from the essential amino acid phenylalanine by the enzyme phenylalanine hydroxylase. Noradrenaline is synthesized from dopamine by dopamine b-hydroxylase and is converted to adrenaline by phenylethanolamine N-methyltransferase (Fig. 2.1). The natural stereoisomers are L-(-)-(R)-noradrenaline and adrenaline.
The occurrence of depression with asthma is very common, especially in women, and can influence behavioral factors, such as treatment compliance, self-assessment, and management of environmental triggers, that can collectively result in poor asthma management and control. This review
describes the association and major clinical implications of stress, anxiety, and depression, and the associated hormonal changes frequently seen in women with poorly controlled asthma. Several validated instruments have recently been developed for screening patients for depression that can
now be used and benefit patients with asthma by earlier detection of these confounding risk factors. The review also highlights the need for further delineation and characterization of specific underlying pathophysiologic and immunologic mechanisms responsible for depression in women.
Investigated the memory T-cell proliferative response to several early and late Epstein-Barr virus (EBV) polypeptides. Blood samples were collected twice, 1 mo before a 3-day block of examinations and again on the last day of the exam series. Ss were 25 healthy, EBV seropositive medical students. The proliferative response to 5 of the 6 EBV polypeptides significantly decreased during examinations. In addition, Ss high (above the median) in seeking support, as measured by the COPE, had lower proliferative responses to 3 EBV polypeptides (p17, p52/50, and p85), as well as higher levels of antibody to EBV virus capsid antigen. The data provide further evidence that psychological stress can modulate the cellular immune response to latent EBV. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Experiments in vitro suggest that although interleukin 5 (IL-5) stimulates the late stages of eosinophil differentiation, other cytokines are required for the generation of eosinophil progenitor cells. In this study transgenic mice constitutively expressing the IL-5 gene were established using a genomic fragment of the IL-5 gene coupled to the dominant control region from the gene encoding human CD2. Four independent eosinophilic transgenic lines have thus far been established, two of which with 8 and 49 transgene copies, are described in detail. These mice appeared macroscopically normal apart from splenomegaly. Eosinophils were at least 65- and 265-fold higher in blood from transgenics, relative to normal littermates, and approximately two- or sevenfold more numerous relative to blood from mice infected with the helminth Mesocestoides corti. Much more modest increases in blood neutrophil, lymphocyte, and monocyte numbers were noted in transgenics, relative to normal littermates (less than threefold). Thus IL-5 in vivo is relatively specific for the eosinophil lineage. Large numbers of eosinophils were present in spleen, bone marrow, and peritoneal exudate, and were highest in the line with the greatest transgene copy number. Eosinophilia was also noted in histological sections of transgenic lungs, Peyer's patches, mesenteric lymph nodes, and gut lamina propria but not in other tissues examined. IL-5 was detected in the sera of transgenics at levels comparable to those seen in sera from parasite-infected animals. IL-3 and granulocyte/macrophage colony-stimulating factor (GM-CSF) were not found. IL-5 mRNA was detected in transgenic thymus, Peyer's patches, and superficial lymph nodes, but not in heart, liver, brain, or skeletal muscle or in any tissues from nontransgenics. Bone marrow from transgenic mice was rich in IL-5-dependent eosinophil precursors. These data indicate that induction of the IL-5 gene is sufficient for production of eosinophilia, and that IL-5 can induce the full pathway of eosinophil differentiation. IL-5 may therefore not be restricted in action to the later stages of eosinophil differentiation, as suggested by earlier in vitro studies.
This study assessed the psychosocial modulation of cellular immunity in 34 medical-student volunteers. The first blood sample was obtained 1 month before examinations, and the second on the day of examinations. There were significant declines in the percentage of helper/inducer T-lymphocytes, in the helper/inducer-suppressor/cytotoxic-cell ratio, and in natural killer-cell activity in the blood samples obtained on the day of examinations. Half of the subjects were randomly assigned to a relaxation group which met between sample points; the frequency of relaxation practice was a significant predictor of the percentages of helper/inducer cells in the examination sample. Three biochemical nutritional assays (albumin, transferrin, and total iron-binding protein) were within normal limits on both samples. Data from the Brief Symptom Inventory showed significantly increased global self-rated distress associated with examinations in the no-intervention group, compared to nonsignificant change in the relaxation group. Clinical and theoretical implications are discussed.
Airway hyperresponsiveness leading to subepithelial fibrosis is mediated by inflammatory cells activated by T helper (Th) 2-derived cytokines such as IL-4 and IL-5. By analyzing the phenotype and response of human lung fibroblasts derived from either fetal (ICIG7) or adult (CCL202) tissue as well as from a Th2-type stromal reaction (FPA) to IL-4 and IL-13, we provide evidence that human lung fibroblasts may behave as inflammatory cells upon activation by IL-4 and IL-13. We show that the three types of fibroblasts constitute different populations that display a distinct pattern in cell surface molecule expression and proinflammatory cytokine and chemokine release. All fibroblasts express functional but different IL-4/IL-13 receptors. Thus, while IL-4 receptor (R) alpha and IL-13Ralpha1 chains are present in all the cells, CCL202 and FPA fibroblasts coexpress the IL-13Ralpha2 and the IL-2Rgamma chain, respectively, suggesting the existence of a heterotrimeric receptor (IL-4Ralpha/IL-13Ralpha/IL-2Rgamma) able to bind IL-4 and IL-13. Stimulation with IL-4 or IL-13 triggers in the fibroblasts a differential signal transduction and upregulation in the expression of beta1 integrin and vascular cell adhesion molecule 1 and in the production of IL-6 and monocyte chemoattractant protein 1, two inflammatory cytokines important in the pathogenesis of allergic inflammation. Our results suggest that when activated by IL-4 and IL-13, different subsets of lung fibroblasts may act as effector cells not only in the pathogenesis of asthma but also in lung remodeling processes. They may also differentially contribute to trigger and maintain the recruitment, homing, and activation of inflammatory cells.
The worldwide incidence, morbidity, and mortality of allergic asthma are increasing. The pathophysiological features of allergic
asthma are thought to result from the aberrant expansion of CD4+ T cells producing the type 2 cytokines interleukin-4 (IL-4) and IL-5, although a necessary role for these cytokines in allergic
asthma has not been demonstrable. The type 2 cytokine IL-13, which shares a receptor component and signaling pathways with
IL-4, was found to be necessary and sufficient for the expression of allergic asthma. IL-13 induces the pathophysiological
features of asthma in a manner that is independent of immunoglobulin E and eosinophils. Thus, IL-13 is critical to allergen-induced
asthma but operates through mechanisms other than those that are classically implicated in allergic responses.
Nonpharmacological treatments with little patient cost or risk are useful supplements to pharmacotherapy in the treatment of patients with chronic illness. Research has demonstrated that writing about emotionally traumatic experiences has a surprisingly beneficial effect on symptom reports, well-being, and health care use in healthy individuals.
To determine if writing about stressful life experiences affects disease status in patients with asthma or rheumatoid arthritis using standardized quantitative outcome measures.
Randomized controlled trial conducted between October 1996 and December 1997.
Outpatient community residents drawn from private and institutional practice.
Volunteer sample of 112 patients with asthma (n = 61) or rheumatoid arthritis (n = 51) received the intervention; 107 completed the study, 58 in the asthma group and 49 in the rheumatoid arthritis group.
Patients were assigned to write either about the most stressful event of their lives (n = 71; 39 asthma, 32 rheumatoid arthritis) or about emotionally neutral topics (n = 41; 22 asthma, 19 rheumatoid arthritis) (the control intervention).
Asthma patients were evaluated with spirometry and rheumatoid arthritis patients were clinically examined by a rheumatologist. Assessments were conducted at baseline and at 2 weeks and 2 months and 4 months after writing and were done blind to experimental condition.
Of evaluable patients 4 months after treatment, asthma patients in the experimental group showed improvements in lung function (the mean percentage of predicted forced expiratory volume in 1 second [FEV1] improved from 63.9% at baseline to 76.3% at the 4-month follow-up; P<.001), whereas control group patients showed no change. Rheumatoid arthritis patients in the experimental group showed improvements in overall disease activity (a mean reduction in disease severity from 1.65 to 1.19 [28%] on a scale of 0 [asymptomatic] to 4 [very severe] at the 4-month follow-up; P=.001), whereas control group patients did not change. Combining all completing patients, 33 (47.1%) of 70 experimental patients had clinically relevant improvement, whereas 9 (24.3%) of 37 control patients had improvement (P=.001).
Patients with mild to moderately severe asthma or rheumatoid arthritis who wrote about stressful life experiences had clinically relevant changes in health status at 4 months compared with those in the control group. These gains were beyond those attributable to the standard medical care that all participants were receiving. It remains unknown whether these health improvements will persist beyond 4 months or whether this exercise will prove effective with other diseases.
Recent findings indicate that the immune and neuroendocrine systems interact and modulate one another functionally. The mechanism for this seems to be that the 2 systems share a set of receptors and ligands (hormones). Cells of the immune system are able to synthesize neuroendocrine peptide hormones which are biologically active and produced in physiologically significant quantities. Furthermore, leukocytes possess functional receptors for these same neuroendocrine hormones which will specifically modulate immune responses. The structural and functional evidence for these interactions is reviewed and discussed in the context of a bidirectional regulatory circuit between the immune and neuroendocrine systems.
Studies of human IgE synthesis are summarized and provide further insight into the cellular and molecular mechanisms involved in IgE regulation, as well as in the alterations responsible for IgE disregulation in some pathological conditions. These include the demonstration that IL-4 is the essential factor for the induction of human IgE syntheses. Another T cell-derived lymphokine, IFN-γ negatively regulated the IgE synthesis induced by IL-4. These two lymphokines can be produced by different T helper cells, as shown in mice, but they can also be the product of the same T cells clones. Additional cellular and/or molecular signals appear to be involved in the IL-4-induced IgE synthesis, but their precise role in this process is undetermined. Finally, alternations of one or more of these regulatory mechanisms can be detected in patients with pathological conditions characterized by hyperproduction of IgE. In particular, the increased prevalence of T cells clones able to produce IL-4 appears to be a distinctive feature of patients with common atopy whereas a reduction in the proportion of IFN-γ-producing T cells seems to be peculiar of both patients with hyper-IgE syndrome and patients with AIDS.
We compared virus-specific antibody and T-cell responses to influenza virus vaccination in 32 caregivers of Alzheimer's disease (AD) patients and matched control subjects. Caregivers showed a poorer antibody response and virus-specific T-cell response following vaccination compared to the control subjects as measured by fourfold increases in antibody titers to the vaccine and lower levels of virus-induced IL-2 levels in vitro. We performed a second study in which forty-eight medical students were inoculated with a series of three injections of the hepatitis-B (HEP-B) vaccine to coincide with the third day of three, three-day examination blocks. Twelve of the 48 medical students seroconverted after the first injection; these students were characterized by falling into the lower stressed/lower anxiety group of students. Students who reported greater social support and lower anxiety and stress demonstrated a higher antibody response to the vaccine and a more vigorous T-cell response to HEP-B surface antigen at the end of the third examination experience. The differences in antibody and T-cell responses to HEP-B and influenza virus vaccinations provide a demonstration of how stress may be able to alter both the cellular and humoral immune responses to vaccines and novel pathogens in both younger and older adults.
The cytokine secretion profiles of T cell lines (TCL) specific for purified proteinderivative (PPD) or streptokinase (SK), contemporarily derived from nine atopic and nine nonatopic individuals, were compared. Upon stimulation with phorbol myristate acetate(PMA) plus anti-CD3 monoclonal antibody (mAb), all TCL from both atopics and nonatopics produced interleukin (IL)-2 and interferon (IFN)-γ. The mean IL-2 production by PPD- or SK-specific TCL from both atopics andnonatopics was similar, whereas the mean IFN-γ production by TCL derived from atopics was significantly lower. In addition, both PPD- and SK-specific TCL from atopics produced detectable amounts of IL-4 and IL-5, whereasthe corresponding TCL derived from nonatopics did not.
A total number of 107 and 99 PPD-specific CD4+ T cell clones (TCC)were then derived from TCL of 4 atopic and 4 nonatopic donors and assessed for their profile of cytokine production in response to stimulation with either PMA plus anti-CD3 mAb or the specific antigen. Under both these experimental conditions, virtually all PPD-specific TCC from both atopic and nonatopic individuals produced IL-2 and IFN-γ. In contrast, the great majority of PPD-specific TCCderived from nonatopic individuals did not produce IL-4 and IL-5, whereashigh proportions of PPD-specific TCC derived from atopic donors displayed the ability to produce noticeable amounts of IL-4 and IL-5 besides IL-2 and IFN-γ.
These data indicate that CD4+ T cells from atopic individuals are able toproduce IL-4 and IL-5 in response to bacterial antigens, such as PPDand SK, that usually evoke responses with a restricted type-1 T helper (Th1)-like cytokine profile in nonatopic individuals. Aberrant IL-4 production by Th cells may represent one of the immune alterations responsible for enhanced IgE antibody production in atopic people.
Biopsy specimens were obtained from the bronchial or the nasal mucosa of three patients with grass pollen-induced bronchial asthma or rhinitis 48 h after positive bronchial or nasal provocation test with grass pollen extract. T cell clones (TCC), derived from these and control specimens, were then assessed for their phenotype, allergen-specificity, profile of cytokine secretion and ability to provide B cell help for IgE synthesis. Out of 50 and 61 CD4⁺ TCC derived from the bronchial mucosa of the two patient with atopic asthma 11 (22%) and 19 (31%), respectively, showed both proliferation and cytokine production in response to grass pollen allergens under major histocompatibility complex-restricted conditions. Of these 21 (70%) exhibited a clear-cut type 2 T helper (Th2) profile and induced IgE synthesis in autologous peripheral blood B cells in the presence of grass allergens. All the other 9 grass-specific clones showed a Th0 pattern of cytokine secretion, but only 1 provided moderate help for IgE synthesis. In contrast, the majority of TCC, derived under the same experimental conditions from the bronchial mucosa of two nonatopic patients with toluene diisocyanate-induced asthma, were CD8⁺ and most of them produced interferon-γ or interferon-γ and interleukin-5, but not interleukin-4, in response to nonspecific stimulation. Of 22 CD4+ TCC 3 (14%) derived from the grass-stimulated mucosa of the patient with allergic rhinitis, but none of those derived from the unstimulated nostril of the same patient, exhibited proliferation and cytokine production in response to grass allergens. All had a clear-cut Th2 profile and provided help for IgE synthesis by autologous B cells.
The functional specialization of T effector cells according to cytokine secretion patterns has been recognized as an important parameter shaping local immune responses. Here we discuss evidence that T cell subsets might also develop distinctive properties related to homing and trafficking into inflamed sites. First, ligands for the inflammation-induced endothelial selectins were found to be induced by IL-12, and hence selectively expressed on Th1 cells generated in vitro. However, their expression on effector cells occuring in vivo is less well correlated with the Th subset. Second, a variety of receptors for and responses towards chemokines have been found to be differentially associated with Th subsets. Notably CCR5 and, to a lesser degree CXCR3 were preferentially found on Th1 cells, CCR4, CCR8 and, more controversial, CCR3 and CXCR4 on Th2 cells. Although many points, such as stability of the phenotype versus dependency on inducing cytokines and activation stages remain to be clarified, it appears that this field provides new insights into the regulation of locally balanced activities of Th subsets and might constitute a promising field for the development of new immunosuppressive drugs.
The mechanisms of stress-related immune alterations have not been fully elucidated. Cell-mediated immune responses as well as antibody and certain cytokines are reported as being suppressed during times of high stress. However, the role of suppression vs dysregulation has not been established in human stress models. The effect of exam stress on regulatory cytokines in 16 healthy medical students was assessed by measuring type-1 (IFN-γ) and type-2 (IL-10) cytokines from 72-h PHA/PMA-stimulated PBMC 4 weeks before and 48 h after exams. Results demonstrated decreased IFN-γ accompanied by increased IL-10 during exam stress that resulted in a decreased IFN-γ:IL-10 ratio. There was a significant correlation between the cytokine response to PHA/PMA and number and subjective adjustment to daily hassles. Additionally, students who reported greater levels of loneliness also reported greater numbers of and poorer subjective adjustment to hassles. The differences were consistent in both males and females but did not correlate with AM cortisol levels. Additionally, when individuals were grouped into high vs low preexam hassle levels, the type-1/type-2 shift in the IFN-γ:IL-10 ratio occurred in the low hassles group only. These data suggest that psychologically stressful situations shift type-1/type-2 cytokine balance toward type-2 and result in an immune dysregulation rather than overall immunosuppression. This may partially explain the increased incidence of type-2-mediated conditions such as increased viral infections, latent viral expression, allergic/asthmatic reactions, and autoimmunity reported during periods of high stress.
Integration of the hypothalamo–pituitary–adrenal stress response occurs by way of interactions between stress-sensitive brain circuitry and neuroendocrine neurons of the hypothalamic paraventricular nucleus (PVN). Stressors involving an immediate physiologic threat (`systemic' stressors) are relayed directly to the PVN, probably via brainstem catecholaminergic projections. By contrast, stressors requiring interpretation by higher brain structures (`processive' stressors) appear to be channeled through limbic forebrain circuits. Forebrain limbic sites connect with the PVN via interactions with GABA-containing neurons in the bed nucleus of the stria terminalis, preoptic area and hypothalamus. Thus, final elaboration of processive stress responses is likely to involve modulation of PVN GABAergic tone. The functional and neuroanatomical data obtained suggest that disease processes involving inappropriate stress control involve dysfunction of processive stress pathways.
Clinical observations and studies of asthmatic patients have often concluded that therre is a strong relationship between the degree of the patient's anxiety and the medical intractability of his illness. However, psychotherapeutic interventions designed to alleviate patient anxiety have been noticeably inconsistent in achieving meaningful alleviation of the patient's asthma. The present paper addresses this apparent paradox by positing the existence of two types of anxiety: a) asthma-specific anxiety, as indexed by Panic-Fear symptomatology scores of the Asthma Symptom Checklist; and b) characterological and pervasive anxiety, as indexed by Panic-Fear personality scores of the Minnesota Multiphasic Personality Inventory. In this study, long term medical outcome was found to be influenced by the combination of these types of anxiety. Wehn high asthma-specific anxiety coexisted with high characterological anxiety, medical outcome following intensive long term medical treatment was exceptionally poor. In contrast, when high asthma-specific anxiety coexisted with average levels of characterological anxiety, medical outcome was exceptionally good. These results are discussed relative to the theoretical distinctions between signal anxiety and anxiety concomitant with a lack of basic ego resources.
Ley's (Behaviour Research and Therapy, 27, 549-554, 1989) dyspnea-fear theory was tested on three groups of subjects: 10 with panic disorder, 24 with asthma, and 12 who were nonanxious and nonasthmatic, using measures of pulmonary function, muscle tension; and self-report measures of generalized anxiety, dyspnea, and psychopathology. Results are supportive of dyspnea-fear theory for asthmatics but not for individuals with panic disorder. Differences between groups on panic/fear measures were explained by a combination of general anxiety and dyspnea. Within-group regression analyses showed that only generalized anxiety symptoms contributed significantly to scores on the Asthma Symptom Checklist scale of panic/fear within the panic disorder group; while only dyspnea contributed to panic/fear among asthmatics. Additional results show that panic disorder subjects performed normally on pulmonary function tests but reported respiratory symptoms as severe as did asthmatics. Compared with normal subjects, both patient groups displayed lower correlations between self-rated symptoms of bronchoconstriction and objective pulmonary measures. Panic disorder subjects showed a negative relationship between pulmonary function and hyperventilation symptoms, suggesting a heightened sensitivity to, and discomfort with, sensations associated with normal pulmonary function. Asthmatics displayed a significant relationship between degree of airway obstruction and both trapezius surface EMG and ratings of hyperventilation symptoms.
The production of interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN gamma) and blast transformation in peripheral blood mononuclear cells were assessed in medical students writing an academic examination. Blood samples were obtained on three occasions: (1) 1 month prior to the examination during a period of relatively low academic demand; (2) immediately after the examination; and (3) 10 days later. Results indicated that immune responses were significantly different immediately after the examination compared with the baseline and postexam measures. Lymphocyte responsiveness to both concanavalin A and pokeweed mitogen was decreased, as was the production of IFN gamma, supporting earlier reports of immunosuppression after relatively commonplace stressors. In contrast to predictions, IL-1 beta production was significantly elevated after the examination. Cortisol levels were also measured, but did not change across the three sample points. Our finding of an increase in IL-1 beta production suggests that stress may have different effects on different cell populations by enhancing the responses of monocytes and depressing those of lymphocytes.
This study used a year-long prospective design to assess linkages among distress, immunity, and illness. Serial blood samples were collected from 40 first-year medical students at the first, third, and fifth examination periods, as well as 1 month before each. There were significant decrements in the production of gamma-interferon by concanavalin A-stimulated lymphocytes obtained at the time of examinations. Antibody titers to Epstein-Barr virus (EBV) increased during examination periods, suggesting reactivation of latent EBV and therefore poorer cellular immune control of latent virus. We obtained data that suggest that T-cell killing by memory T lymphocytes of EBV transformed autologous B lymphocytes also declined during examination periods. The activity of a lymphokine, leukocyte migration inhibition factor, normally suppressed during recrudescence of herpes simplex virus type 2 infections, was altered during examination periods and an increase in both plasma and intracellular levels of cyclic AMP associated with examination stress was observed. An increase in the incidence of self-reported symptoms of infectious illness was also associated with examination periods. The data support the linkage between stress-related immunosuppression and health.
Cell-mediated immune responses were studied in 12 Antarctic and sub-Antarctic wintering groups at quarterly intervals over the period 1984-1992, using the cutaneous CMI Multitest. These populations are among the most isolated on earth. While the sub-Antarctic population at Macquarie Island had levels of responsiveness and hypoergy (9%) comparable to healthy populations in temperate zones, the Antarctic Continental group showed a level of hypoergy of 36%. There was no seasonal variation in the pattern of responses. It is concluded that the extreme and isolated environment and stress factors are responsible for the decreased immunological responsiveness but the mechanisms are presently unclear. On review, one factor appears to be perceived anxiety. The high rate of hypoergy in Antarctica, where medical care is limited, may have health implications. These groups provide an excellent analogue for immunological investigations in longer term space flight.
The nervous system can generate outflow capable of signaling cells of the immune system via two routes: (1) hormonal influences via hypothalamopituitary-target organ activation, and (2) neurotransmitter influences via direct innervation of the parenchyma of both primary and secondary lymphoid organs. Both noradrenergic and neuropeptidergic nerve fibers are found directly adjacent to cells of the immune system in bone marrow, thymus, spleen, lymph nodes, and other sites. These neurotransmitters can modulate immune responsiveness at several levels, including individual cellular functions, collective cellular interactions and immune responses, and overall host immunological response to a challenge by bacteria, viruses, tumor cells, or other sources. The ability of neural signals to modulate immune responsiveness is influenced by such factors as co-localization with other neurotransmitters, synergistic or dual signaling by neurotransmitters and cytokines, hormonal influences on ligand availability or receptor responsiveness, extent of catabolism and inactivation of the neural signal, and unique chemical and morphological aspects of the specific compartmentation of the lymphoid organ in which signaling is taking place. Thus, neural-immune signaling is a complex and dynamic process, with bidirectional interactions in a complex microenvironment.
Biological hypersensitivity is the fundamental feature of atopy, and patients suffering from this syndrome are characterized by their ability to produce high levels of IgE in response to low amounts of antigen. This hypersensitivity results in a range of acute and chronic diseases, such as asthma, rhinitis, allergic conjunctivitis and atopic dermatitis. In addition to their biological effects, these diseases may have psychological consequences in terms of stress, anxiety or depression. However, atopic patients, far from displaying a typical depressive psychological profile, are characterized by their increased emotional sensitivity. Atopic individuals alert us to the presence of allergens but perhaps they also indicate something about our way of life. Are the symptoms displayed by allergic patients, their wheezing, sneezing or itching skin, more than a simple biological response?
We have examined whether the local eosinophilia provoked by inhalational allergen challenge of patients with atopic asthma is associated with the appearance, in vivo, of activated TH2-type T helper lymphocytes.
Fifteen patients with atopic asthma had bronchial wash and bronchoalveolar lavage (BAL) 24 hours after allergen or diluent challenge separated by at least 21 days.
There was an increase in eosinophils in both bronchial wash (p = 0.01) and BAL (p = 0.02) after allergen challenge but not after diluent challenge. Activation of CD4+ BAL T cells was suggested by an increase in the expression of CD25 shown by flow cytometry after allergen challenge, when compared with diluent (p = 0.02). There was no evidence of activation of CD8 T cells. By in situ hybridization after allergen challenge as compared with diluent, increases were shown in the numbers of cells expressing mRNA for interleukin-4 (IL-4) (p = 0.005), IL-5 (p = 0.01), and granulocyte-macrophage colony-stimulating factor (p = 0.03) but not IL-3, IL-2, or interferon-gamma. In situ hybridization of BAL cells after immunomagnetic separation of CD2-positive and CD2-negative cell populations showed that IL-4 and IL-5 mRNAs were associated with T lymphocytes after allergen challenge. BAL and bronchial wash eosinophilia closely correlated with maximal late fall in forced expiratory volume in 1 second after allergen challenge.
Cytokines produced by activated TH2-type CD4+ T cells in the airway may contribute to late asthmatic responses by mechanisms that include eosinophil accumulation.
This article presents a new formulation of the relationship between stress and the processes leading to disease. It emphasizes the hidden cost of chronic stress to the body over long time periods, which act as a predisposing factor for the effects of acute, stressful life events. It also presents a model showing how individual differences in the susceptibility to stress are tied to individual behavioral responses to environmental challenges that are coupled to physiologic and pathophysiologic responses.
Published original articles from human and animal studies and selected reviews. Literature was surveyed using MEDLINE.
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Stress is frequently seen as a significant contributor to disease, and clinical evidence is mounting for specific effects of stress on immune and cardiovascular systems. Yet, until recently, aspects of stress that precipitate disease have been obscure. The concept of homeostasis has failed to help us understand the hidden toll of chronic stress on the body. Rather than maintaining constancy, the physiologic systems within the body fluctuate to meet demands from external forces, a state termed allostasis. In this article, we extend the concept of allostasis over the dimension of time and we define allostatic load as the cost of chronic exposure to fluctuating or heightened neural or neuroendocrine response resulting from repeated or chronic environmental challenge that an individual reacts to as being particularly stressful.
This new formulation emphasizes the cascading relationships, beginning early in life, between environmental factors and genetic predispositions that lead to large individual differences in susceptibility to stress and, in some cases, to disease. There are now empirical studies based on this formulation, as well as new insights into mechanisms involving specific changes in neural, neuroendocrine, and immune systems. The practical implications of this formulation for clinical practice and further research are discussed.
This review of the empirical literature on the relationship between asthma and emotion presents an explanatory model of the connection between them. Asthmatics tend to report and display a high level of negative emotion, and asthma exacerbations have been linked temporally to periods of heightened emotionality. Causality may be bidirectional. Hypothesized mediators for the relationship between asthma and emotionality include vagal and alpha-sympathetic hyperreactivity, predominant obstruction in the larger airways, individual response stereotypy, direct effects of emotion-related facial muscle tension on the airways, the emotional effects of asthma medications, heightened respiratory drive, and hyperventilation. Predictions are presented for research on this model of asthma and emotion, and for the psychological treatment of asthma.
The present study focused on the relationship between psychological stress and immune reaction to a novel antigen. Participants completed questionnaires on daily hassles, psychoneurotic complaints, coping style, and loneliness, 2 and 6 months after the first of a series injections with a low dose recombinant DNA hepatitis B vaccine. Antibody response was determined 7 months after the first vaccination. Based on the psychological questionnaires two different stress measures were calculated: a Stress Index score-month-2 and a Stress Index score-month-6 indicating stress levels experienced at the beginning and at the end of the study respectively. Antibody levels were found to be negatively related with the Stress Index score-month-2. Although the influence of psychological stress reported on month 6 tended to be in the same direction, this effect was not significant. Coping styles and loneliness were not associated with antibody formation. These results suggest that antibody formation to rDNA hepatitis B vaccine is negatively influenced by psychological stress.
A first-time parachute jump was chosen as a model to evaluate the endocrine response to acute psychological stress. In 43 inexperienced tandem parachutists, blood was drawn continuously from 2 h before to 1 h after the jump and analyzed at 10-min intervals for plasma concentrations of epinephrine (E), norepinephrine (NE), cortisol, GH, PRL, and TSH. In addition, heart rate was recorded throughout the experiment. There was a significant increase in heart rate and E concentrations during the jump itself. NE, cortisol, GH, PRL, and TSH peaked with a latency of 10-20 min. Apart from cortisol and TSH concentrations, which were still elevated 1 h after the stress event, plasma levels of the other endocrine variables normalized within 1 h following the jump. Statistically significant cross-correlations could be observed between E and NE (r = 0.60, no time lag) and between E and PRL (r = 0.58, 10-min time lag) only. Even in a very homogenous group of subjects and under well-controlled conditions, endocrine responses to acute psychological stress show considerable variations.
The influence of academic examinations on immunity and lung function was investigated in 64 adolescents to determine if stress-related changes would differ between healthy and asthmatic students. Blood samples were collected on three occasions: 1 month prior, during, and 2-3 weeks after exams. Leukocyte subsets were enumerated, and in vitro assays were conducted to assess lymphocyte proliferative and cytolytic responses and neutrophil production of superoxides. Examinations elicited significant changes in several lymphocyte subsets and marked alterations in the three functional measures in all students. However, the magnitude and pattern of change did not differ between healthy and asthmatic students. Similarly, neither mild nor more severe asthmatics showed an exam-related decrement in lung function, as reflected by peak expiratory flow rate. This research validated that examinations are a salient cause of altered immune responses, but indicates that there is not a concomitant aggravation of inflammatory disease in well-managed asthmatics.
The expression of IL-4 and IL-13 was analyzed in a panel of short ragweed allergen (Amb a 1)–specific T-cell clones from an allergic subject and a nonallergic individual. The T cells from the allergic subject showed a predominantly T
H0 phenotype. The T cells from the nonallergic individual produced undetectable levels of IL-4 and high levels of interferon-γ, suggesting a T
H1 cytokine profile. However, all T-cell clones showed significantly higher levels of IL-13 secretion than IL-4 secretion, and no quantitative correlation could be found between the levels of IL-4 and IL-13 in the clones tested. Furthermore, both cytokines showed similar kinetics of expression in antigen-induced steady-state messenger RNA. Finally, both cytokines were induced by stimulation of the cells with either ionomycin alone or with a combination of ionomycin and phorbol myristate acetate. These results demonstrate that there is a significant clonal diversity and quantitative difference in the levels of IL-4 and IL-13 expression in allergen-specific human T cells. (J Allergy Clin Immunol 1996;98:1035-44.)
Studies have demonstrated a weak correlation between the degree of airways obstruction and the severity of asthma symptoms. Although the causes for this disparity are probably multiple, mood has been hypothesized to modulate symptoms. This investigation was designed to evaluate the effect of mood and other patient characteristics on the perception of airways obstruction.
We compared mood variables, symptom severity, albuterol use, and peak expiratory flow rate (PEFR) measured three times daily over a 21-day period in 21 adults with moderate to severe asthma. Electronic equipment was used for data collection. Analyses included both individual patient assessments and a within-subjects, time series, pooled regression of concurrent and time-lag data.
After pooling 1323 observations, there was a weak concurrent relationship between symptoms and PEFR (beta = -0.17, p < 0.001). Only five patients (24%) were accurate perceivers, defined by a statistically significant relationship between symptoms and PEFR across time. Higher forced expiratory flow at 25% to 75% of capacity predicted perception accuracy (p = 0.004); active mood was marginally associated with accuracy (p = 0.06). These two variables together explained 41% of the variation in perception accuracy (p = 0.004). Mood did not independently predict symptoms, but conversely, increased symptoms predicted less pleasant mood (beta = 0.08, p < 0.001), less active mood (beta = -0.11, p < 0.001), and less active-pleasant mood (beta = 0.06, p < 0.001). PEFR did not predict mood, and only pleasant mood independently predicted higher PEFR (beta = 0.04, p < 0.05). Symptoms, but not PEFR, were concurrently associated with albuterol use (beta = 0.24, p < 0.001).
The relationship between changes in PEFR and symptoms over time was generally poor. Those patients with lower FEF25-75 values tended to be less accurate perceivers. Mood states were influenced by asthma symptoms, but the converse was not true.
The relative contribution of IL-4 and IL-13 to the regulation of IgE synthesis has remained relatively poorly characterized, partially because of lack of suitable animal models. We have studied the roles of IL-4 and IL-13 in human IgE synthesis induced by supernatants derived from activated CD4+ or CD8+ T cell clones. Neutralizing anti-IL-4 and anti-IL-13 monoclonal antibodies (mAbs) inhibited IgE synthesis induced by anti-CD40 mAbs and supernatants from CD4+ T cells by an average 61% and 42%, respectively (n = 25). Recombinant IL-13 had additive effects on IL-4-induced IgE synthesis, but only when IL-4 was present at low concentrations. Accordingly, IL-4 was the dominant IgE synthesis-inducing cytokine derived from highly polarized T helper (TH)2 cells. However, anti-IL-13 mAbs also significantly inhibited IgE synthesis induced by two of three supernatants derived from allergen-specific T(H2)-like cell lines generated from the skin of patients with atopic dermatitis. Furthermore, anti-IL-13 mAbs almost completely inhibited IgE synthesis induced by supernatants from T(H1) cells or CD8+ T cell clones. Taken together, these data indicate that IL-13, in addition to IL-4, contributes to IgE synthesis induced by all T helper cell subsets, including allergen-specific T(H2) cells. Moreover, IL-13 appears to be the major IgE synthesis-inducing cytokine derived from T(H1) cells or CD8+ T cells.
Although a variety of factors are responsible for atopic dermatitis (AD), very little is known about the effect of stress caused by a natural disaster on AD symptoms.
This study was conducted to assess the effect of stress or trauma on the symptoms of AD.
One thousand four hundred fifty-seven patients with AD (745 males and 712 females), diagnosed by using the criteria of the Japanese Dermatology Association, were enrolled in the study. The data were obtained from a self-administered questionnaire given to patients with AD after experiencing the Great Hanshin Earthquake. The data were analyzed by multivariate logistic regression analysis. Patients were divided into 3 groups: area A, severe damage to buildings and houses; area B, mild damage; and control area, no damage.
Exacerbation of skin symptoms was found in 38% and 34% of patients in areas A and B, respectively, whereas similar exacerbation was seen in 7% of control patients. Nine percent and 5% of the patients in areas A and B, respectively, showed improvement in their symptoms compared with 1% in the control group. The earthquake caused stress in 63% and 48% of the patients in areas A and B, respectively, but fewer patients felt stress in undamaged areas (19%). Multiple logistic regression analysis revealed that of the factors examined here, subjective distress is the factor that is most responsible for the exacerbation of skin symptoms (odds ratio, 2.98; 95% confidence interval, 2.25-3.96).
The results presented here strongly suggest that stress caused by a natural disaster influences AD symptoms.
Objective:
This short review surveys our current knowledge on the development and heterogeneity of human mast cells, the distribution of mast cells within human skin and the properties of human skin mast cells both in vitro and in vivo. It also examines the effects of antihistamines in the wheal-and-flare response in the skin provoked by bradykinin.
Results:
Mast cells derive from mononuclear precursor cells which undergo their final phase of their differentiation in the tissues. In normal skin, mast cells, which are primarily of the MC(TC) subtype, occur in the greatest density in the superficial dermal zone. Like all other mast cells, human skin mast cells bind IgE with high affinity to specific FcepsilonRI receptors, but unlike those from lung, tonsils, adenoids or intestine, they also express the C5a receptor (CD88) and activation sites for substance P, VIP, somatostatin, and compound 48/80. Both IgE-dependent stimulation by activating tyrosine kinases, and non-immunologic stimulation by activating G-proteins induce a characteristic compound exocytosis resulting in the liberation of the preformed mediators. Production of prostaglandin D2 and leukotriene C4, however, occurs only with IgE-dependent stimulation. In vivo, dermal microdialysis and scanning laser Doppler imaging have been used to assess the role of histamine in the wheal-and-flare response. These techniques were also used to show that low concentrations of intradermal bradykinin release negligible quantities of histamine. The results showed that although the resultant flare was inhibitable by antihistamines, low concentrations of bradykinin released negligible quantities of histamine. This suggests a potentially novel mechanism of action of antihistamines that requires further detailed investigation.
Stress is a condition of human existence and a factor in the expression of disease. A broader view of stress is that it is not just the dramatic stressful events that exact their toll but rather the many events of daily life that elevate activities of physiological systems to cause some measure of wear and tear. We call this wear and tear "allostatic load," and it reflects not only the impact of life experiences but also of genetic load; individual habits reflecting items such as diet, exercise, and substance abuse; and developmental experiences that set life-long patterns of behavior and physiological reactivity (see McEwen). Hormones associated with stress and allostatic load protect the body in the short run and promote adaptation, but in the long run allostatic load causes changes in the body that lead to disease. This will be illustrated for the immune system and brain. Among the most potent of stressors are those arising from competitive interactions between animals of the same species, leading to the formation of dominance hierarchies. Psychosocial stress of this type not only impairs cognitive function of lower ranking animals, but it can also promote disease (e.g. atherosclerosis) among those vying for the dominant position. Social ordering in human society is also associated with gradients of disease, with an increasing frequency of mortality and morbidity as one descends the scale of socioeconomic status that reflects both income and education. Although the causes of these gradients of health are very complex, they are likely to reflect, with increasing frequency at the lower end of the scale, the cumulative burden of coping with limited resources and negative life events and the allostatic load that this burden places on the physiological systems involved in coping and adaptation.
Allergic asthma is a complex and heterogeneous disease which is characterized by intermittent reversible airway obstruction, chronic inflammation of the airways, bronchial hyperreactivity and an infiltration of lymphocytes and eosinophils into the airway submucosa. Animal models and clinical studies in humans have indicated an important role for T helper type 2 lymphocytes, producing IL-4, IL-5 and IL-13, in the pathogenesis of this disorder. However, although IL-4 and IL-13 have strong anti-inflammatory properties, the physiologic anti-inflammatory Th2 response does not seem to be operational in allergic asthma. Moreover, the induction of a Th1 response seems to aggravate, rather than ameliorate, its inflammatory character. This article will focus on the involvement of T lymphocyte subpopulations in the pathogenesis of allergic asthma and allergic diseases. In addition, a potential role of the subpopulation(s) of T regulatory cells in the induction and/or maintaince of the disease process will be discussed.
In the last few years strong evidence has accumulated to suggest that allergen-reactive type-2 T helper (T(H)2) cells play an important role in the induction and maintenance of the allergic inflammatory cascade. First, cytokines and chemokines produced by T(H)2 cells (GM-CSF, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, macrophage-derived chemokine) and those produced by other cell types in response to T(H)2 cytokines or as a reaction to T(H)2-related tissue damage (eotaxin, transforming growth factor-beta, IL-11) account for most pathophysiologic aspects of allergic disorders (production of IgE antibodies; recruitment or activation of mast cells, basophils, and eosinophils; mucus hypersecretion; subepithelial fibrosis; and tissue remodeling). The T(H)2 hypothesis may also explain the complex genetic background responsible for allergic disorders. Several genes are involved in the development and regulation of T(H)2 cells and may provide the reason why the prevalence of atopic allergy is increasing in Western countries. Indeed, a dramatic change has occurred in the last several decades in the "microbial" environment of children, thus probably altering the balance between T(H)1 and T(H)2 responses to "innocuous" antigens (allergens) in favor of T(H)2 responses. Finally, the T(H)2 hypothesis offers exciting opportunities for the development of novel immunotherapeutic strategies targeted to address allergen-specific T(H)2 cells or T(H)2-derived effector molecules in atopic individuals.
Asthma is common in children and its prevalence in this age group is increasing. While the reasons for this reported increase, and indeed the true magnitude of the increase, remain unclear, there can be no doubt that asthma is now a major health problem in children worldwide. Fortunately, our knowledge of the pathophysiology of asthma is also increasing. It is now known that asthma is a chronic inflammatory disease regulated by a variety of mediators, of which perhaps the leukotrienes are among the most important. This new understanding of the pathophysiology of the disease has spurred the development of the antileukotriene agents, which can be expected to play an increasingly important role in the management of childhood asthma.