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Effects of Sleep and Sleep Loss on Immunity and Cytokines
Abstract
Sleep is hypothesized to be a restorative process that is important for the proper functioning of the immune system. Severity of disordered sleep in depressed- and alcoholic subjects correlates with declines in natural- and cellular immunity and is associated with alterations in the complex cytokine network. Sleep loss has a role in mediating these immune changes as experimentally induced partial night sleep deprivation replicates the kind of sleep loss found in clinical samples and induces a pattern of immune alterations similar to that found in depressed- and alcoholic patients. Despite evidence that sleep and sleep loss have effects on immune processes and nocturnal secretion of cytokines, the clinical significance of these immune changes is not known. Moreover, in view of basic evidence of a reciprocal interaction between sleep and cytokines, further research is needed to understand whether alterations in cytokines contribute to disordered sleep in patient populations.
... It has been suggested that the stress of sleep loss may evoke sub-optimal host defence which may increase the risk of illness, infection, decrease effective wound healing and increase the susceptibility to sepsis (Costa et al., 2010;Shephard et al., 1998). Although, it has been suggested that disturbed sleep may cause declines in natural and cellular immunity as well as alterations in the complex cytokine network (Irwin, 2002), unfortunately, the vast majority of research performed on sleep disturbances have only utilized in vitro methods of assessing immune function (Dinges et al., 1994;Dinges et al., 1995;Moldofsky et al., 1989;Palmblad et al., 1976;Palmblad et al., 1979). Similarly, prolonged exercise is believed to adversely affect immune function (Gleeson, 2007). ...
... A stimulatory effect of sleep deprivation on sleep-regulating cytokines (e.g. IL-1β, TNFα and IFNγ) and stress hormones (Dickstein and Moldofsky, 1999;Hu et al., 2003;Radomski et al., 1992) may mediate the altered immune response which in turn might increase susceptibility to infection (Dinges et al., 1995;Irwin, 2002). ...
... Although it has been suggested that disturbed sleep may cause declines in natural and cellular immunity, as well as alterations in the complex cytokine network (Irwin, 2002), unfortunately, the vast majority of research performed on sleep disturbances have only utilized in vitro methods of assessing immune function (Dinges et al., 1994;Dinges et al., 1995;Moldofsky et al., 1989;Palmblad et al., 1976;Palmblad et al., 1979). Relatively few studies have examined the in vivo immune response to disrupted sleep. ...
The purpose of this thesis was to examine the effects of various stressors on thermoregulation and immune function, and to examine the functional link between these two systems, utilizing conventional, as well as novel techniques and methods in humans. Wireless iButtons® were found to provide a novel, valid and reliable alternative for the measurement of human skin temperature measurement, of particular utility when other currently available methods would prove to be problematic. Prolonged exercise impaired in vivo T-cell-mediated immunity. Contact sensitization with the antigen diphenylcyclopropenone was found to provide a simple, inexpensive, and robust method for research investigators to evaluate the effects of stress on immune function in vivo. Furthermore, a plateau in the contact hypersensitivity response can be attained with repeated serial administration of the antigen, allowing for the utilization of the contact hypersensitivity method in future repeated-measures, cross-over designed research investigations. Two nights of total sleep deprivation, with or without energy restriction, did not significantly impair thermoregulation during prolonged cold exposure, and therefore, does not appear to increase the risk of hypothermia. Three nights of sleep disruption did not significantly affect core temperature at rest or in response to exercise-heat-stress. However, disrupted sleep of this duration does appear to alter heat loss pathways, with blunted forearm sweating and increases in upper-body skin temperature, with no increase in thermal strain. Three nights of sleep disruption significantly enhances in vivo T-cell-mediated immunity, but does not affect individual in vitro immune indices, and suggests that in vitro markers may not reveal the true effect of stressors on the coordinated immune response. Alterations in skin temperature due to disrupted sleep, lend evidence to the functional, mechanistic coupling between circadian variations in skin temperature and skin immune function, whereby prolonged periods of increased skin blood flow provides for the maintenance of skin immunity.
... Cytokines and their receptors are constitutively expressed in the central nervous system, where they contribute to the regulation / modulation of multiple physiologic and behavioral processes, including sleep-wake behavior (Irwin, 2002;Imeri and Opp, 2009;Irwin and Opp, 2017;Krueger et al., 2001). IL-1β and TNF-α are the most studied cytokines within the context of sleep, and they and their receptors are expressed in neurons in brain regions involved in the regulation of sleepwake behavior (Breder et al., 1993(Breder et al., , 1988Imeri and Opp, 2009). ...
... Many studies demonstrate that these inflammatory mediators, particularly IL-1β and TNF-α, increase non-rapid eye movements sleep (NREMS) when administered centrally or peripherally (Krueger et al., 2001). IL-1β and TNF-α participate in the regulation of normal, physiological sleep in the absence of pathology; in the alterations in sleep that occur after acute or chronic sleep loss; and during inflammatory pathologies such as infections or trauma (Irwin, 2002;Irwin and Opp, 2017;Rowe and Griesbach, 2022). ...
... While different aspects of sleep play an important role in immune responses to vaccination (Irwin, 2002;Bryant et al., 2004;Irwin, 2015;Castrucci, 2018;Besedovsky et al., 2019;Zimmermann and Curtis, 2019), conflicting results have been observed in regard to their influence on the immunogenicity of influenza vaccines. For example, healthy adults (18 -55 years of age) who slept less than 7 hours per night had an increased likelihood of developing symptomatic illness following viral exposure (Cohen et al., 2009;Prather et al., 2015). ...
... The interplay between sleep and the immune system is intricate (Irwin, 2002;Bryant et al., 2004;Irwin, 2015) and the mechanisms underlying the impact of inadequate sleep on inflammatory and antiviral responses have not been fully elucidated. Sleep disruption is thought to affect the regulation of immune system, primarily by altering activity of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, which in turn results in potentiated transcription of proinflammatory genes and inhibited transcription of antiviral gene programs (Irwin, 2019). ...
Background
The reduced effectiveness of standard-dose influenza vaccines in persons ≥65 years of age led to the preferential recommendation to use high-dose (HDFlu) or MF59-adjuvanted (MF59Flu) vaccines for this age group. Sleep is an important modulator of immune responses to vaccines and poor sleep health is common in older adults. However, potential effects of poor sleep health on immune responses to influenza vaccination in older adults remain largely unknown.
Methods
We conducted a cohort study of 210 healthy participants age ≥65 years, who received either seasonal high-dose (HDFlu) or MF59-adjuvanted (MF59Flu) influenza vaccine. We assessed sleep characteristics in this cohort by standardized questionnaires and measured the antibody titer against influenza A/H3N2 virus in serum of study participants by hemagglutination inhibition assay on the day of immunization and 28 days thereafter. We then assessed the association between sleep characteristics and antibody titers.
Results
Our results demonstrated that male, but not female, study participants with excessive daytime sleepiness had an impaired influenza A/H3N2-specific antibody response at Day 28 post-vaccination. No other associations were found between antibody titer and other sleep characteristics, including sleep quality and obstructive sleep apnea.
Conclusion
Our results provide an additional and easily measured variable explaining poor vaccine effectiveness in older adults. Our results support that gaining sufficient sleep is a simple non-vaccine interventional approach to improve influenza immune responses in older adults. Our findings extend the literature on the negative influence of excessive daytime sleepiness on immune responses to influenza vaccination in older male adults.
... erefore, an in-depth study of the pathogenesis of insomnia is required to improve the efficacy of clinical treatments and the quality of life of patients. Clinical studies have found that lack of sleep can lead to an increase in the number of monocytes, systemic regulation of inflammatory factors, and aggravation of immune dysfunction [1][2][3][4]. Lack of sleep can also activate spontaneous innate immunity and STAT family proteins [5]. e mechanism by which immune mediators produced during sleep deprivation destroy the blood-brain barrier, regulate nerve activity, and contribute to nerve damage is poorly understood. ...
... e immune system plays an important role in the relationships between sleep, health, and neurodevelopment [24,25]. Clinical data show that sleep disorders, including insomnia, can cause immune dysfunction [1][2][3][4]. Sleep deprivation may increase the risk of inflammation and infection by altering immune function, whereas napping or extending sleep can restore immune system homeostasis [26,27]. Various studies have reported that microglia became activated in the brains of sleep-deprived mice, and the number and morphology of microglia were significantly positively correlated with neuronal apoptosis [28,29]. ...
Objective:
Microglial BV-2 cells are activated in the brain following insomnia. Naringin (NAR) is a polymethoxylated flavonoid that is also commonly found in citrus fruits and is known for its antioxidant potential. However, the effect of NAR on microglial cells has rarely been studied in the brain of an organism after insomnia. This study aimed to investigate the effects and potential mechanisms of action of NAR on microglial cell activation and inflammation.
Methods:
BV-2 cells were obtained from the China Center for Type Culture Collection and randomly divided into five treatment groups: control, model, NAR (10 μM), WP1066 (5 μM), and NAR + WP1066. With the exception of the control group, all groups were stimulated with LPS (1 μg/mL) for 6 h. CCK8 was used to quantify cell viability and a scratch test was performed to detect cell migration. The expression levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), nterleukin 10 (IL-10), and insulin like growth factor (1IGF-1) were measured by ELISA. Western blotting was performed to determine the levels of p-STAT3 and p-JAK. The Focalcheck™ Thin-Ring Fluorescent Microspheres kit was used to detect cell phagocytosis. Immunofluorescence was used to observe the expression of iNOS and arginase1 in BV-2 cells.
Results:
Compared with the control group, cell migration, cell viability, and the expression of IL-1β, IL-6, TNF-α, and iNOS were significantly increased in the model group, whereas the expression levels of IL-10, IGF-1, and arginase 1, as well as cell phagocytosis were reduced. With the increase in NAR concentration, cell migration, cell viability, the expression levels of IL-1β, IL-6, TNF-α, and iNOS decreased, while the expression of IL-10, IGF-1, and arginase 1 increased. Compared with the control group, p-STAT3, and p-JAK expression in the model group were significantly increased (P<0.05). Compared with the model group, the expression of p-STAT3 and p-JAK in the NAR, NAR + WP1066, and WP1066 groups was significantly decreased (P < 0.05).
Conclusion:
NAR treatment inhibited the proliferation, migration, and inflammation of BV-2 cells as well as the activation of microglia to the M1 phenotype. Conversely, NAR treatment promoted the activation of microglia to the M2 phenotype and enhanced the phagocytic function of BV-2 cells by regulating the activity of the JAK/STAT3 pathway.
... Sleep is essential for human beings, occupying a significant portion of the lifespan and playing a critical role in the restoration and maintenance of various physiological systems such as the immune system, brain metabolism, endocrine functions, and metabolic processes (4)(5)(6). sleep problems are linked to imbalance of energy and hormonal disturbances, inflammation and inflammatory disease, such as obesity, diabetes, cardiovascular disease and decline in kidney function and increase chronic kidney disease (7)(8)(9)(10)(11)(12). ...
Background
The current study aimed to evaluate the association between the intake of plant-based protein, animal-based protein, total protein, and the ratio of plant to animal protein with sleep quality and quality of life in patients undergoing hemodialysis.
Methods
In this cross-sectional study, 479 adult patients undergoing dialysis for a minimum of 3 months were included. The dietary intake was calculated using information from a validated 168-item semi-quantitative food frequency questionnaire. Quality of life (QOL) was assessed using the Kidney Disease Quality of Life Short Form (KDQOL-SF 1.3). and the Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality.
Results
In this study, the mean age of the participants was 58.18 years (± 14.25 years), with the majority being male (58.2%). After adjusting for potential confounders, significant positive associations were observed between total protein intake (β = 0.12, p = 0.03) and quality of life (QOL). Conversely, there were significant negative associations between the ratio of plant to animal protein intake (β = −0.94, p < 0.01) and QOL. Furthermore, significant negative associations were found between total protein intake (β = −0.02, p < 0.05) and animal protein intake (β = −0.19, p < 0.05) with poor sleep quality. Additionally, there were significant positive associations between the ratio of plant to animal protein intake (β = 0.188, p < 0.05) and poor sleep quality.
Conclusion
Increased consumption of animal protein is associated with improved sleep quality and Quality of Life (QOL) in patients undergoing hemodialysis (HD). Further research, especially prospective studies, is required to confirm these associations.
... IL-6 is also related to sleep quality. Sleep loss results in excessive IL-6 secretion during the day, and daytime IL-6 plasma concentration inversely correlates with the quantity of slow wave sleep [33,34]. In addition, subcutaneous administration of IL-6 prior to sleep initiation in healthy subjects led to delayed REM sleep latency and decreased REM sleep duration, with no alteration in the total amount of NREM sleep [35]. ...
Sleep regulates inflammatory responses, and the innate immune system affects sleep. Interleukin-1 beta, tumor necrosis factor alpha, growth hormone-releasing hormone, prolactin, and nitric oxide are somnogenic substances. Sleep deprivation, such as chronic insomnia or obstructive sleep apnea, affects cytokine production, glial function, natural killer cell activity, and inflammasome function. This review will discuss the relationship between sleep and innate immunity.
... During the pandemic, achieving good quality sleep was essential for COVID-19 patients as it improved patients' quality of life, their mental health, and played an important role in preserving immune function, thus reducing the transmission of viral infections [9,10]. Especially for patients with severe COVID-19, decreasing sleep quality may increase dyspnea by aggravating preexisting hypoxemia and hypercapnia as well as increase patients' anxiety and depression levels [11]. ...
... 10,[13][14][15] Along the same lines, data are available showing that the administration or induction of proinflammatory cytokines leads to increased symptomatology also in healthy humans [16][17][18] and that elevated inflammation is detected in non-cancer populations with emotional distress syndromes. 19,20 However, cancer-related inflammation seems to be linked with more prolonged and more severe symptoms among cancer patients compared to individuals without a history of cancer, suggesting a precipitating role for treatments (particularly chemo-, radiation-, hormone-, or immunotherapy and targeted agents), potentially triggering a hyperactivated cross-signaling and feedforwarding enhanced inflammatory cascades. 12 Mounting evidence has also pointed at cancer-related inflammation as an accelerator of physiological aging through sustained cellular damage and stress. ...
... Chronic sleep deprivation can lead to conditions such as decreased alertness and responsiveness, slower cognitive processes, depressed mood, and poor concentration [8,9]. Sleep quality and duration affects cellular immunity and cytokine levels, and even mild sleep deprivation can compromise a person's immunity [10,11]. Sleep disorders are also associated with metabolic changes, increased caloric intake, and obesity [12,13]. ...
Background
According to statistics, about one-fifth of the world's elderly people suffer from sleep disorders, and the problem of sleep disorders in the elderly is extremely serious, and this problem is one of the important causes of chronic diseases such as hypertension, hyperlipidemia, diabetes mellitus, and coronary heart disease in the elderly. The positive effect of Tai Chi exercise therapy on sleep problems has been confirmed, but at present, the effect of the specific duration of Tai Chi exercise on the improvement of elderly people with moderate to severe sleep disorders varies.
Objective
META analysis was used to investigate and find that long-term Tai Chi exercise therapy has the best effect on improving sleep in elderly patients with moderate to severe sleep disorders. Methods: META analysis was performed using Revman 5.3 after searching Web of science, Pubmed, Scopus, The Cochroae Library, OVID, CBM, CNKI, VIP, and other databases, and then filtering and extracting.
Results
A total of seven papers were included. Meta-analysis showed that tai chi exercise was more effective in improving sleep problems in elderly patients with sleep disorders compared to the control group, and the difference was significant. This was demonstrated by a decrease in the global Pittsburgh Sleep Quality Index (PSQI) score [SMD = −0.66, 95 % CI (−0.91, −0.41), P < 0.00001], as well as its subdomains of subjective sleep quality [SMD = −0.79, 95 % CI (−1.06, −0.52), P < 0.00001], sleep latency [SMD = −0.80, 95 % CI (−1.21, −0.40), P < 0.00001], sleep duration [SMD = −0.38, 95 % CI (−0.72, −0.04), P = 0.03], habitual sleep efficiency [SMD = −0.58, 95 % CI (−0.84, −0.31), P < 0.0001], sleep disturbance [SMD = −0.51, 95 % CI (−0.78, −0.25), P = 0.00001] and daytime dysfunction [SMD = −0.33, 95 % CI (−0.59, −0.07), P = 0.01]. Improvement was also observed in the Epworth Sleepiness Scale (ESS) and Insomnia Severity Index Scale (ISI). The results showed that the optimal duration and frequency of Tai Chi exercise therapy for improving moderately severe elderly patients with sleep disorders was long-term.
Conclusion
This study systematically assessed the efficacy of Tai Chi exercise therapy for elderly patients with moderate-to-severe sleep disorders. Through a meta-analysis of relevant randomized controlled trials (RCTs), it aims to determine the effectiveness of Tai Chi exercise in improving sleep quality in elderly patients with moderate-to-severe sleep disorders, as well as to compare its effects with those of traditional treatments; to analyze the safety of Tai Chi exercise for this patient population and assess its feasibility as a non-pharmacological therapy; and to fill the research gaps and provide more comprehensive and systematic evidence support. This study provides a practical approach to reducing the risk of medication side effects in older adults with sleep disorders and offers a potentially effective non-pharmacological treatment option, especially for those who are unable or unwilling to use medication. Tai chi exercise may not only improve sleep, but also improve coordination, muscle strength, balance, and reduce stress and anxiety in older adults. It also helps older adults socialize and enhances their social connections and emotional support. This study suggests that community centers or activity centers for the elderly can organize tai chi classes to promote the participation of older adults, and can be used as a scientific exercise rehabilitation tool in clinical treatment, incorporating tai chi practice into daily life, such as tai chi practice at a fixed time every day or every week, which not only helps to improve the sleep disorders of older adults, but also improves their overall quality of life.
... This suggests a role of sleep loss in these immune changes. We don't yet know the clinical importance of these immunological alterations, although research suggests that sleep and sleep loss affect immune mechanisms and nocturnal cytokine production (60). Bahumutrata stands for polyurea or frequent urination. ...
Background: Subgrouping of diseased population, based on Deha-Prakriti (DP), phenotypic classification of Ayurveda will explore the variation in the disease severity, which further aid in the management of the disease more precisely and selectively. But there is a paucity in the data generation. Amavata (~Rheumatoid Arthritis) is one of such diseases, resulting from the conglomeration of Ama and aggravated Vata gets lodged in the joints. Aim & Objective: To evaluate variations in the severity of symptoms, duration of morning stiffness, DAS28 (Disease Activity Score in 28 Joints), and Disability Index (DI) among different Vata predominant Deha-Prakriti (DP) individuals of Amavata (~Rheumatoid Arthritis). Materials & Methodology: The study was conducted among 155 clinically diagnosed patients of Amavata, who were screened for DP assessment through the CCRAS-PAS scale. Those who were found to have Vata predominant DP were sub-grouped into Single Vataja (V), Vata-Pittaja (VP), and Vata-Kaphaja (VK) DP, based on the proportion of the doshas in the output of scale. Demographic profile, the severity of the symptoms, duration of the morning stiffness, DAS28, and DI were assessed and calculated using SPSS software version 20.0, p≤0.05 was considered statistically significant. Results: Kruskal-Walli’s test revealed that Single Vata predominant DP patients were found to have severe Sandhi-shula (Joint pain) (p<0.0001), Shunatanga (Numbness of the joint) (p-value at 0.0069), Nidra-Viparyaya (Irregular sleep patterns) (p-value at 0.0012) than VP and VK DP individuals. Sandhi-Shotha (Joint swelling) (p-value at 0.0299), Angamarda (generalized body pains) (p-value at 0.0130), Alasya (laziness) (p<0.0001), Gaurava (Heaviness) (p<0.0001), and Apaka (delayed digestion) (p-value at 0.0254) were found severe in VK DP, whereas Trishna (Thirsty) (p<0.0001), Nidraviparyaya (p-value at 0.0012) were more severe in VP DP individuals. One-way ANOVA revealed that the duration of morning stiffness (2.03±0.2 hours, p-value at 0.446), DAS28 (6.85±0.175, p-value at 0.0035), and DI (1.87±0.54, p-value at 0.0003) were found significantly high in single Vataja than VP and VK Deha-Prakriti. Conclusion: The disease severity in terms of duration of morning stiffness, DAS28, and DI were found more severe in Single Vataja DP. The severity of the signs and symptoms also varied according to DP.
... Research studies suggest that chronic sleep disturbance or deprivation in humans can lead to neurocognitive dysfunction, sustained immune activation, and alterations of circulating levels of inflammatory markers (Irwin, 2002(Irwin, , 2019Garbarino et al., 2021;Westermann et al., 2015;Born et al., 1997a). Our NHP results support the above findings. ...
Sleep deprivation in humans is associated with both cognitive impairment and immune dysregulation. An animal model of neuropathogenesis may provide insight to understand the effects of sleep deprivation on the brain. Human neurocognition is more closely mirrored by nonhuman primates (NHP) than other animals. As such, we developed an NHP model to assess the impact of sleep deprivation on neurocognition and markers of systemic immune activation. Six male rhesus macaques underwent three rounds of sleep deprivation (48 h without sleep) at days 0, 14, and 28. We performed domain specific cognitive assessments using the Cambridge Neuropsychological Test Automated Battery (CANTAB) via a touch screen before and after 24 and 48 h of sleep deprivation. Immune activation markers were measured in the blood by multiplex assay and flow cytometry. Although we observed variability in cognitive performance between the three rounds of sleep deprivation, cognitive impairments were identified in all six animals. We noted more cognitive impairments after 48 h than after 24 h of sleep deprivation. Following 48 h of sleep deprivation, elevations in markers of immune activation in the blood were observed in most animals. The observed impairments largely normalized after sleep. The co-occurrence of systemic immune alterations and cognitive impairment establishes this model as useful for studying the impact of sleep deprivation on neurobehavior and immune perturbations in rhesus macaques.
... Additionally, growing evidence suggests that sleep is closely associated with immune function (Everson, 1993;Everson and Toth, 2000;Al-Abri et al., 2023). Severe sleep disorder reduces natural and cellular immunity by inducing alterations in the cytokine network (Irwin, 2002). Xu et al. (2020) showed that sleep deprivation further enhances the LPS-mediated upregulation of proinflammatory cytokine levels in plasma and the hippocampus of adult mice, suggesting that sleep deprivation exacerbates LPSinduced inflammation. ...
Objective
Studies have suggested that prenatal exposure to inflammation increases the risk of neuropsychiatric disorders, including anxiety, depression, and cognitive dysfunction. Because of anatomical and hormonal alterations, pregnant women frequently experience sleep dysfunction, which can enhance the inflammatory response. The aim of this study was to explore the effects of maternal sleep deprivation on prenatal inflammation exposure-induced behavioral phenotypes in offspring and identify the associated mechanisms.
Methods
Pregnant mice received an intraperitoneal injection of lipopolysaccharide (LPS) on gestational day 15 and were subsequently subjected to sleep deprivation during gestational days 15–21. Anxiety-like behavior was evaluated by the open field test and the elevated plus maze test. Depression-like behavior was assessed by the tail suspension test and the forced swimming test. Cognitive function was determined using the Morris water maze test. The levels of markers of inflammation and synaptic function were examined employing general molecular biological techniques.
Results
The results showed that prenatal exposure to LPS resulted in anxiety- and depression-like symptoms and learning and memory deficits, and these effects were exacerbated by maternal sleep deprivation. Furthermore, maternal sleep deprivation aggravated the prenatal LPS exposure-induced increase in the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α and decrease in the levels of postsynaptic density-95 and synaptophysin in the hippocampus.
Discussion
Collectively, these results suggested that maternal sleep deprivation exacerbates anxiety, depression, and cognitive impairment induced by prenatal LPS exposure, effects that were associated with an inflammatory response and synaptic dysfunction.
... Sleep and lack of sleep have been reported to play a role in immune processes, such as cellular immune activation and nocturnal and functional secretions of inflammatory biomarkers (1). An inflammatory reaction precedes the development of the metabolic diseases, and certain inflammatory biomarkers can be targeted to prevent the development of inflammatory conditions and organ damage (2). ...
Objectives
Poor sleep behavior can trigger an inflammatory response and contribute to the development of inflammatory diseases. Cytokines can act as indicators of inflammation and may precede the onset of inflammatory diseases. This study aimed to determine the association between sleep timing parameters (bedtime, sleep duration, sleep debt, and social jetlag) and the levels of nine serum and salivary inflammatory and metabolic biomarkers.
Methods
Data were collected from 352 adolescents aged 16–19 years enrolled in Kuwait’s public high schools. The levels of C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), adiponectin, leptin, and insulin were measured from saliva and serum samples. We conducted mixed-effect multiple linear regression modeling to account for the school variable as a random effect to assess the relationship between the sleep variables and salivary and serum biomarkers. Mediation analysis was conducted to check if BMI was a mediator between bedtime and the biomarkers.
Results
There was a statistically significant elevation in serum IL-6 level associated with later bedtime (0.05 pg./mL, p = 0.01). Adolescents with severe sleep debt of ≥2 h had an increase in salivary IL-6 biomarker levels (0.38 pg./mL, p = 0.01) compared to those who had sleep debt of <1 h. Adolescents with sleep debt of ≥2 h had significantly higher levels of serum CRP (0.61 μg/mL, p = 0.02) than those without sleep debt. Additionally, we found that the inflammatory biomarkers (CRP, IL-6, IL-8, IL-10, VEGF, and MCP-1) and metabolic biomarkers (adiponectin, leptin, and insulin) had more statistically significant associations with the bedtime variables than with sleep duration variables. CRP, IL-6, and IL-8 were associated with sleep debt, and IL-6, VEGF, adiponectin, and leptin levels were associated with social jetlag. BMIz was a full mediator in the relationship between late bedtime and increased serum levels of CRP, IL-6, and insulin.
Conclusion
Adolescents who go to bed at or later than midnight had dysregulated levels of salivary and serum inflammatory biomarkers, suggesting that disrupted circadian rhythm can trigger higher levels of systemic inflammation and potentially exacerbate chronic inflammation and the risk of metabolic diseases.
... Sleep is vitally important state helping to restore the immune, nervous, skeletal, and muscular systems that maintain mood, memory, and cognitive function (Carskadon and Dement, 2005;Krueger et al., 2016). Promoted by the internal circadian clock, sleep is a naturally recurring state of the mind and body, characterized by altered consciousness, relatively inhibited sensory activity and reduced muscle activity (Sejnowski and Destexhe, 2000;Irwin, 2002;Wagner et al., 2004). Sleep usually occurs as a relatively long overnight process in which the brain goes through several different sleep stages (Romero et al., 2003;Acharya et al., 2005;Ermis et al., 2010;Imperatori et al., 2021;Patel et al., 2022). ...
The human brain presents a heavily connected complex system. From a relatively fixed anatomy, it can enable a vast repertoire of functions. One important brain function is the process of natural sleep, which alters consciousness and voluntary muscle activity. On neural level, these alterations are accompanied by changes of the brain connectivity. In order to reveal the changes of connectivity associated with sleep, we present a methodological framework for reconstruction and assessment of functional interaction mechanisms. By analyzing EEG (electroencephalogram) recordings from human whole night sleep, first, we applied a time-frequency wavelet transform to study the existence and strength of brainwave oscillations. Then we applied a dynamical Bayesian inference on the phase dynamics in the presence of noise. With this method we reconstructed the cross-frequency coupling functions, which revealed the mechanism of how the interactions occur and manifest. We focus our analysis on the delta-alpha coupling function and observe how this cross-frequency coupling changes during the different sleep stages. The results demonstrated that the delta-alpha coupling function was increasing gradually from Awake to NREM3 (non-rapid eye movement), but only during NREM2 and NREM3 deep sleep it was significant in respect of surrogate data testing. The analysis on the spatially distributed connections showed that this significance is strong only for within the single electrode region and in the front-to-back direction. The presented methodological framework is for the whole-night sleep recordings, but it also carries general implications for other global neural states.
... Two of the leading causes of mortality in patients with ESRD on dialysis are cardiovascular disease and infection [32]. Sleep disorders are associated with adverse effects on blood pressure control, cardiac remodeling, and immune function, which would lead one to anticipate higher mortality rates in this population [15,33]. One possible explanation for this finding is that patients with sleep disorders and ESRD are seeing medical professionals more often due to their dialysis. ...
Increased risk of all-cause mortality not accounted for by traditional cardiovascular risk factors has been linked to chronic kidney disease. This study tested the hypothesis that mortality may be greater in patients with end-stage renal disease (ESRD) and a sleep disorder diagnosis. The United States Renal Data System database was queried to determine the effect of sleep disorder diagnoses on mortality in ESRD patients enrolled between 2004 and 2015. Sleep disorders were identified using International Classification of Diseases-9 and -10 codes. Mortality risk associated with sleep disorders was examined using Cox proportional hazards (CPH) modeling. In the final CPH model, sleep disorder diagnoses were associated with decreased risk of mortality, with hazard ratios (and 95% confidence intervals) for insomnia, hypersomnolence, restless leg syndrome, and obstructive/central sleep apnea of 0.76 (0.75–0.76), 0.81 (0.78–0.84), 0.79 (0.77–0.80), and 0.82 (0.81–0.82), respectively. Black or other race and Hispanic ethnicity, and to a small extent, female sex and increasing Charlson comorbidity index, were also associated with decreased risk, whereas increasing age, hemodialysis (versus peritoneal dialysis) and catheter or graft access type were associated with increased risk. This study suggests that the diagnosis of a sleep disorder may be associated with improved survival in ESRD patients.
... There is increasing evidence supporting an association between sleep and immune function as well as inflammatory response. For example, sleep deprivation decreased NK cell, T cell, and monocyte function [19], and increased the secretion of cytokines, such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1, and IL-2 [20,21]. It is generally known that HIV infection is characterized by destruction of the immune system and disruption of inflammatory response. ...
Objective: Our goal was to estimate the pooled prevalence of self-reported sleep disturbances in HIV-infected people through meta-analysis, taking into account variations in geographic region, gender, age group, CD4 counts, and instrument used to measure sleep disturbances. Methods: The authors conducted systematic searches of PubMed and PsycINFO to include studies that met our criteria. A random effect meta-analysis model was used to estimate the pooled prevalence of self-reported sleep disturbances in HIV-infected people. The potential moderators of self-reported sleep disturbances were explored with meta-regression analysis. Results: Twenty-seven articles comprising a total of 9246 HIV-positive participants were finally included in our analysis. The overall prevalence of self-reported sleep disturbances in HIV-infected people was 58.0% (95% CI = 49.6-66.1). Meta-regression analysis indicates that geographic region, gender, and instrument significantly explain part of the heterogeneity of the prevalence estimates between the included studies. Conclusion: The findings suggest that HIV-infected people suffer from a heavy burden of sleep disturbances. It is therefore recommended that sleep quality should be routinely assessed in HIV-infected people in order to identify the medical treatment needs and the potential impact of sleep problems on antiretroviral therapy outcomes in this population.
... The frontline health workforce is experiencing a high volume of work and multiple psychosocial stressors which may influence their mental and emotional health, leading to burnout symptoms. Sleep deprivation and a critical lack of psychosocial support may aggravate such symptoms amidst COVID-19 18 sleep disturbances may end up hampering the immune response that is so vital for fighting diseases. 19 ...
Background: The stress that the present global pandemic of COVID-19 has generated in every aspect of human life can be managed by activities such as meditation and mindfulness, especially among healthcare practitioners, patients, and caregivers, as well as the common man during times of crisis. Objective: To discuss the psychological impact of COVID-19 and the role of mindfulness in reducing stress and improving psychological health among caregivers and healthcare professionals. Method: We collected around 68 reviewed articles from electronic databases such as PubMed, EBSCO, CNAHIL, and Google scholar using the search terms COVID-19, stress, mindfulness, school teachers, parents and health care professionals burnout, and sleeplessness. Thirty-seven articles were included after carefully reviewing mindfulness-based stress reduction. The mindfulness-based stress reduction and remaining articles were excluded as the report focuses on caregivers and health care professionals. Results: Mindfulness appears to be an effective intervention to improve mental health, and stress reduction enhances the professional performance of medical health professionals and caregivers. There is a significant reduction in stress among caregivers, parents and health care professionals. Conclusion: Mindfulness is a safe, practical, integrative approach to reducing stress. Caregivers and healthcare providers experiencing stress or stress‐related symptoms benefit from mindfulness-based programs.
... Sleepiness is regulated in humans by two main processes: the circadian process, which 2 makes us sleepier in the night, and the homeostatic process, which causes sleepiness to 3 increase with time awake [1]. It has been proposed that interleukin-6, a pleiotropic 4 cytokine, participates in circadian sleepiness regulation by increasing at night in the 5 blood and inducing sleepiness through signalling in the brain [2][3][4][5][6]. Early studies of 6 diurnal variation of IL-6 in humans found a peak in the night-time [7,8], and it is this 7 observational relationship that forms the main line of evidence for a regulatory effect of 8 circulating IL-6 on sleepiness. ...
The pleiotropic cytokine interleukin-6 (IL-6) has been proposed to contribute to circadian regulation of sleepiness by increasing in the blood at night to signal for sleepiness. Earlier studies have reported diurnal variations of IL-6, but phase estimates are conflicting. We have therefore performed a meta-analysis on the diurnal variation of circulating IL-6. Studies were included if they reported circulating levels of IL-6 recorded at least twice within 24 hours in the same individual. A systematic search resulted in the inclusion of 43 studies with 56 datasets, for a total of 1100 participants. Individual participant data were available from 4 datasets with a total of 56 participants. Mixed-effects meta-regression modelling confirmed that IL-6 varied across the day, the most conspicuous effect being a trough in the morning. These results stand in contrast to earlier findings of a peak in the evening or night, and suggest that diurnal variation should be taken into account in order to avoid confounding in studies of IL-6 in plasma or serum.
... Both sleep loss, a common consequence of poor sleep quality, and GI conditions may be associated with increased systemic inflammation [84,85]. The relationship between insomnia and IBD in particular may be explained by common inflammatory pathways, including through C-reactive protein and interleukin-6 [11,[85][86][87][88][89][90]. Finally, it is also important to note that there can be pharmacological contributions to the sleep/GI relationship. ...
Purpose of Review
This review addresses the relationship between sleep and chronic, painful, gastrointestinal (GI) conditions.
Recent Findings
Similar to other chronic physical or mental health conditions, there is an increased prevalence of sleep concerns among individuals with chronic digestive conditions. The relationship between sleep and GI symptom experience is bidirectional. Poor sleep quality results in increased sensitivity to visceral pain and/or increased likelihood for certain diseases to flare/relapse while, simultaneously, the presence of painful gastrointestinal symptoms may also disrupt sleep. Sleep disorders and GI conditions may have shared cognitive, behavioral, psychosocial, circadian, and genetic mechanisms including hyperarousal, psychiatric comorbidity, and circadian misalignment.
Summary
There is a bidirectional relationship between sleep and chronic GI conditions, which is impacted by cognitive, behavioral, psychosocial, genetic, and circadian mechanisms.
... For instance, it has been found that sleep enhances the production of Il-2 by T cells, 13,14 while sleep deprivation leads to a decreased Il-2 production from stimulated lymphocytes under the influence of the hypothalamic-pituitaryadrenal axis. 15 Moreover, another study showed that five days of sleep deprivation decrease circulating Il-2 and Il-6, which is similar to the effects of acute sleep deprivation and psychological stress. 16,17 On the other hand, earlier studies indicated that nocturnal sleep deprivation leads to daytime (post-deprivation period) over-secretion of Il-6 in healthy subjects, and there is a negative correlation between nocturnal sleep and Il-6 release. ...
Sleep is an imperative physiological aspect that plays a vital role in maintaining hormonal and humeral functions of the body and hence a healthy life. Circadian rhythms are daily oscillations in human activities and physiology that prepare human beings to better react to and anticipate challenges in the surrounding environment, which are a consequence of diurnal changes of day and night. The sleep/wake cycle is one of the most prominent manifestations of the circadian rhythm and communicates tightly with the immune system with daily oscillation of immunity. Sleep deprivation is now recognized as a common condition inherent to modern society, and it is detrimental to certain body functions, particularly immune function. The aim of this review is to explore the role of sleep in maintaining a healthy immune system during the COVID-19 pandemic. The review discusses sleep-regulatory substances that are linked to host defense mechanisms such as interleukin-1β, interleukin-6, tumor necrosis factor alpha, and interferon gamma. Cytokine levels also fluctuate with sleep/wake homeostasis and our review explores the relationship between sleep and cytokines and proposed therapeutics. The review will also cover sleep and immune response in children, adolescents, and healthcare workers, and finally it will touch on the effect of obstructive sleep apnea on immune response and the severity of COVID-19.
... Sleep disturbances in healthy adults induce inflammation [21][22][23][24][25][26][27][28][29][30][31], characterized, in part, by increased production of IL1β, IL6, and TNFα. This inflammatory response is likely mediated by reactive microglia. ...
Microglia play a critical role in the neuroimmune response, but little is known about the role of microglia in sleep following an inflammatory trigger. Nevertheless, decades of research have been predicated on the assumption that an inflammatory trigger increases sleep through microglial activation. We hypothesized that mice (n = 30) with depleted microglia using PLX5622 (PLX) would sleep less following the administration of lipopolysaccharide (LPS) to induce inflammation. Brains were collected and microglial morphology was assessed using quantitative skeletal analyses and physiological parameters were recorded using non-invasive piezoelectric cages. Mice fed PLX diet had a transient increase in sleep that dissipated by week 2. Subsequently, following a first LPS injection (0.4 mg/kg), mice with depleted microglia slept more than mice on the control diet. All mice were returned to normal rodent chow to repopulate microglia in the PLX group (10 days). Nominal differences in sleep existed during the microglia repopulation period. However, following a second LPS injection, mice with repopulated microglia slept similarly to control mice during the dark period but with longer bouts during the light period. Comparing sleep after the first LPS injection to sleep after the second LPS injection, controls exhibited temporal changes in sleep patterns but no change in cumulative minutes slept, whereas cumulative sleep in mice with repopulated microglia decreased during the dark period across all days. Repopulated microglia had a reactive morphology. We conclude that microglia are necessary to regulate sleep after an immune challenge.
... In the hospital setting, disruptions in the sleep-wake cycle contribute to delirium and complicate recovery [16]. Importantly, sleep is involved in the regulation of hormones and neuropeptides related to immune function and wound healing [17,18], processes that are critical for the burn patient. While there is increasing evidence for the effectiveness of non-pharmacologic interventions for sleep disorders in non-burn populations, the literature is limited in burn survivors. ...
Burn injuries are a complex medical condition associated with negative physical and emotional consequences including disturbances in sleep. The goals of this systematic review were to examine the prevalence of sleep disturbances in adult burn survivors and evaluate the effects of intervention to improve sleep. Eight electronic databases were systematically searched and yielded 49 studies (13 interventional and 36 non-interventional). Results from the systematic review demonstrate that a variety of sleep disturbances are common in burn survivors, persisting years after the injury and are associated with pain, itch, emotional distress and reduction in quality of life. Sleep assessment was primarily based on subjective measures and the available data did not allow for assessing the prevalence of sleep disorders in burn survivors. Results of the meta-analysis of four studies demonstrated that a variety of interventions improved sleep quality. These findings provide further evidence that sleep is compromised in burn survivors and highlight the need for ongoing assessment using a combination of validated self-reports and objective measures of sleep. More research is needed to determine the most effective treatments for sleep disorders in burn survivors and if early intervention will serve to improve long term outcomes.
... Sleep disturbance also showed a significant but small effect in this study, consistent with other studies showing that poor sleep quality and short sleep duration are associated with higher CRP concentrations [67,85,86]. Evidence suggests that sleep and the immune system can have bi-directional effects on each other with sleep promoting cytokine expression and cytokines influencing sleep and sleep depth [87,88]. Poor sleep quality, poor sleep continuity, and short sleep duration has been linked to adverse health outcomes and exaggerated inflammatory responses including increases in TNF, IL-6, and CRP. ...
Elevated serum concentrations (>3 mg/L) of the acute-phase protein, C-reactive protein (CRP), is used as a clinical marker of inflammation and is reported to be a strong risk factor for cardiovascular disease. In psychiatric populations, CRP concentration is reported to be higher in depressed versus healthy individuals. Positive associations between CRP and depression have been established in both clinical and community samples, but effect sizes are attenuated after controlling for confounding variables. Similarly, emerging research has begun to draw a link between inflammation, symptoms of anxiety, and substance abuse. Given the high level of comorbid anxiety and substance use disorders in many depressed populations, this study examined whether depression (Patient Health Questionnaire 9 [PHQ-9]) and substance use-related (Drug Abuse Screening Test [DAST]) symptoms were associated with CRP concentrations in the blood after adjusting for relevant medical, social, and demographic covariates in a large sample undergoing screening for several transdiagnostic psychiatric research studies. A total of 1,724 participants were analyzed for association of CRP with variables using multivariate linear regression. An unadjusted model with no covariates showed that PHQ-9 was significantly associated with CRP in All (β = 0.125), Female (β = 0.091), and Male (β = 0.154) participants, but DAST was significantly associated with CRP in males only (β = 0.120). For the adjusted model, in both males and females, mood-stabilizer treatment (β = 0.630), opioid medication (β = 0.360), body mass index (β = 0.244), percent body fat (β = 0.289), nicotine use (β = 0.063), and self-reported sleep disturbance (β = 0.061) were significantly associated with increased CRP concentrations. In females, oral contraceptive use (β = 0.576), and waist-to-hip ratio (β = 0.086), and in males, non-steroidal anti-inflammatory drug use (β = 0.367) were also associated with increased CRP concentrations. There was no significant association between CRP and individual depressive, anxiety, or substance use-related symptoms when covariates were included in the regression models. These results suggest that associations between circulating CRP and the severity of psychiatric symptoms are dependent on the type of covariates controlled for in statistical analyses.
... Sleep disturbances are common in chronic tinnitus and appear associated with tinnitus-related emotional and cognitive distress (Crönlein et al., 2016). Moreover, sleep deprivation strongly affects the immune system, including NK cell number and activity (Irwin, 2002;van Leeuwen et al., 2009). In our sample, 65.9% (N = 27) reported (sometimes) having difficulties falling to sleep because of their tinnitus. ...
Background
Depression and anxiety are known to be associated with stress-induced changes in the immune system. Bothersome tinnitus can be related to stress and often co-occurs with depression and anxiety. This study investigates associations of psychological and audiological tinnitus-related factors with inflammatory parameters and immune cell subsets in chronic tinnitus patients as well as treatment-related effects.
Methods
This longitudinal study of inpatients treated with compact multimodal tinnitus-specific cognitive behavioral therapy included four repeated measurement sessions: baseline (N = 41), treatment end, 7.8-week (N = 35), and 13.8-week follow-up (N = 34). Data collection included audiometric testing, blood sampling, and psychometric questionnaires: Tinnitus Handicap Inventory (THI), Perceived Stress Questionnaire (PSQ-20), and Hospital Anxiety Depression Scale (HADS). Flow cytometry was used to analyze immune cell subsets. Statistical analyses comprised correlation and network analysis (cross-sectional), and linear mixed effect models (longitudinal).
Results
Bootstrapped network analysis showed negative averaged cross-sectional associations of cytotoxic natural killer (NKc) cell frequency (CD56 + CD16+) and PSQ-20 (−0.21 [−0.48, 0]) and of regulatory natural killer (NKreg) cell frequency (CD56 + CD16dim/−) and HADS anxiety (−0.14 [−0.38, 0]). No significant treatment effects were found. A negative predictive effect of baseline PSQ-20 scores (β = −6.22 [−12.18, −0.26], p = 0.041) and a positive predictive effect of baseline ferritin levels (β = 8.90 [2.76, 15.03], p = 0.004) on NKc cell frequency across the repeated measurement sessions were observed.
Conclusion
We observed negative relationships between perceived stress levels and NKc cell frequency and between anxiety levels and NKreg cell frequency in chronic tinnitus patients. These exploratory results suggest stress−/anxiety-related immune alterations in bothersome tinnitus but need to be tested in further confirmatory studies with larger sample sizes. The potential of NK cells as biomarkers of emotional distress in chronic tinnitus should be further investigated.
... Chronic pain (not only chronic lower back pain) has been shown to impact both physical and psychological health as it is likely to be accompanied by decreased movement [41] and walking motion [42], along with higher rates of depression [41,43]. During bouts of lower back pain, the sympathetic nervous system is activated [44], while the continuity of chronic lower back pain can lead to its overactivity, thereby increasing the concentration of inflammatory cytokines in the body [45,46] in a process known to be associated with sleep disorders [47]. Additionally, college students' weekly sitting time is >30 h [48]. ...
Insomnia in college students has a significant impact on academic performance and mental health (e.g., depression). Although the mechanisms underlying insomnia and chronic pain are becoming clearer, only a few studies on college students have examined these factors by their location in the body. The purpose of the present study was to identify the location of chronic pain in the body most associated with insomnia in college students. A web-based survey was used to collect information pertaining to nine questions from 494 university students: sex, age, presence of chronic pain, intensity of chronic pain, location of chronic pain, and duration of chronic pain, as well as scores from the Athens Insomnia Scale (AIS), Pain Catastrophizing Scale, and Hospital Anxiety and Depression Scale. To examine the association between insomnia and the site of chronic pain, stepwise logistic regression analysis was conducted with AIS as the target variable. The results showed a significant positive correlation between chronic pain in the lumbar region and AIS scores. Future longitudinal studies including multiple factors are necessary to clarify the causal relationship between insomnia and chronic lower back pain.
... For example, sleep enhanced the levels of sIL-6R to over 70% of the wake levels at the termination of sleep, and simultaneously induced IL-6 trans-signaling regardless of classical/membrane-bound IL-6 signaling [85]. This process further supports the role of sleep in immune defense [135,136]. ...
The circadian rhythm is an evolutionarily conserved time-keeping system that comprises a wide variety of processes including sleep–wake cycles, eating–fasting cycles, and activity–rest cycles, coordinating the behavior and physiology of all organs for whole-body homeostasis. Acute disruption of circadian rhythm may lead to transient discomfort, whereas long-term irregular circadian rhythm will result in the dysfunction of the organism, therefore increasing the risks of numerous diseases especially cancers. Indeed, both epidemiological and experimental evidence has demonstrated the intrinsic link between dysregulated circadian rhythm and cancer. Accordingly, a rapidly increasing understanding of the molecular mechanisms of circadian rhythms is opening new options for cancer therapy, possibly by modulating the circadian clock. In this review, we first describe the general regulators of circadian rhythms and their functions on cancer. In addition, we provide insights into the mechanisms underlying how several types of disruption of the circadian rhythm (including sleep–wake, eating–fasting, and activity–rest) can drive cancer progression, which may expand our understanding of cancer development from the clock perspective. Moreover, we also summarize the potential applications of modulating circadian rhythms for cancer treatment, which may provide an optional therapeutic strategy for cancer patients.
... Regardless of whether or not self-isolated people build up immunity and remain well, they regularly experience the ill effects of antagonistic mental impacts. Critically, the impacts of psychological well-being and sleep on immunity have been shown in the past studies 9 . ...
Objective:
Worldwide transmission of the novel coronavirus (COVID-19) and related morbidity and mortality has presented a global challenge for several reasons. One such underrecognized and unaddressed aspect is the emotional health problems that medical staff have developed during this pandemic. The purpose of this one-month study was to examine anxiety levels and sleep quality of 100 medical staff members who worked in medical clinics treating COVID-19 patients in Saudi hospitals and to investigate the association of both anxiety levels and sleep quality with age, sex, and distinctive demographics.
Materials and methods:
We investigated anxiety levels and sleep quality of 100 medical staff members (age range 20-60 years) who worked in medical clinics treating COVID-19 patients in Saudi hospitals and the association of both anxiety levels and sleep quality with age, sex, and distinctive demographics. Anxiety levels and sleep quality were measured using the Self-Rating Anxiety Scale and the Pittsburgh Sleep Quality Index (SAS and PSQI, respectively).
Results:
A significant increment in anxiety and poor sleep quality was found in medical staff caring for COVID-19 patients. Anxiety levels in females were higher than males; however, poor sleep quality was somewhat higher in males vs. females but did not vary between age groups. Age was significantly negatively correlated with anxiety symptoms; individuals < 40 years old vs. ≥ 40 had more significant anxiety levels. We observed that medical staff with top-level salaries demonstrated a significant correlation (p = 0.028) between poor sleep quality and ill effects vs. those who had lower pay rates. A correlation between income and anxiety was not found.
Conclusions:
The higher the probability and intensity of exposure to coronavirus patients, the more noteworthy the danger that medical staff will experience the ill effects of mental issues.
The suprachiasmatic nucleus (SCN) is the primary unit of the mammalian circadian rhythm. The generation and coordination of many physiological, endocrine, and behavioural circadian rhythms are crucial (Morin and Blanchard 2001; Nakagawa and Okumura 2010). The suprachiasmatic nucleus (SCN) in humans, as well as in non-human model systems, acts as the neural basis for circadian rhythms. The disturbance of circadian behaviour, which has been clinically recorded, is linked to the participation of the SCN region (Haugh and Markesbery 1983; Schwartz et al. 1987). The decrease in the ability to keep track of circadian rhythms as one gets older has been linked to the deterioration of SCN neurons during the ageing process (Hofman and Swaab 1994; Mirmiran et al. 1992). The suprachiasmatic nucleus (SCN) is a compact anatomical region in the hypothalamus, positioned bilaterally above the optic nerve and close to the third ventricle. The suprachiasmatic nucleus (SCN) functions as the primary controller of the mammalian brain, coordinating and governing the hormonal and behavioural circadian and circannual rhythms (Swaab 2003). Damage to the suprachiasmatic nucleus (SCN) region, such as from tumours in the suprasellar pituitary or metastases, has been reported to decrease the synthesis of a crucial SCN peptide called arginine vasopressin (AVP) and disturb circadian rhythms (Borgers et al. 2011; Swaab 2003). Hence, it is crucial to employ immunocytochemical labelling methodologies utilising antibodies targeting arginine vasopressin (AVP), vasoactive intestinal polypeptide (VIP), or neurotensin to precisely ascertain the identity of this anatomical feature. Mai and his colleagues employed immunocytochemistry to categorise the human SCN into five primary subgroups (Mai et al. 1991). The region of the suprachiasmatic nucleus (SCN) that receives information from the retinohypothalamic tract (RHT) and is crucial for synchronisation is characterised by the existence of VIP neurons (Moore et al. 2002). AVP is found throughout the rest of the suprachiasmatic nucleus (SCN), whereas neurotensin is evenly distributed throughout the entire SCN. The suprachiasmatic nucleus (SCN) consists of fibres that contain somatostatin, thyrotropin-releasing hormone, galanin, preproenkephalin, delta-sleep-inducing peptide, leptin receptor, and hypocretin (Swaab 2003). Furthermore, the human suprachiasmatic nucleus (SCN) has specific sites that bind to vasoactive intestinal peptide (VIP), such as oestrogen receptor (ER) α and β, progesterone receptor (Kruijver and Swaab 2002), and melatonin receptors (MT) (Y.-H. Wu et al. 2013). Considering the existence of VIP in the SCN, it is unsurprising that peptide methionine amide (PHM), a peptide including histidine and methionine, is also present in the human SCN. The PHM and VIP genes are located on adjacent exons of a common prepro-VIP gene. The work conducted by Romijn et al. 1999 employed confocal laser scanning microscopy to identify a small fraction of neurons in the human SCN that showed co-localization with AVP and VIP. Following the application of microwave therapy for antigen retrieval, the detection of AVP and VIP staining exhibits enhanced responsiveness. The quantity of AVP-stained neurons exhibited a 70% rise, whereas the quantity of VIP-stained neurons showed a substantial increase of 280%. The neurons observed before microwave therapy were mainly localised in the central region of the SCN, whereas the neurons that became visible only after microwave treatment were situated in the peripheral area of the SCN. The results suggest that the AVP and VIP neurons in the central part of the SCN have a greater amount of peptide, maybe because they are more active than the peripheral neurons (Hofman and Swaab 1994).
Objectives
Investigate whether partial sleep deprivation for five nights causes vascular changes in healthy university students.
Study design
Prospective observational study.
Methods
The study involved 18 young and healthy university students who were instructed to sleep as recommended for their age group for three consecutive nights. On the study's fourth night, participants slept a maximum of 5 h and, on the following nights, they slept less than 8 h. The assessments consisted of carotid assessment, flow‐mediated dilation, and blood pressure (BP) monitoring. During the 8 days studied, participants used actigraphy in their daily routine.
Results
A decrease in the BP of the common carotid artery (CCA), both systolic and diastolic resulted from partial sleep deprivation. After one night of partial sleep deprivation, there was a significant increase in peak systolic velocity and a significant decrease in the systolic diameter of CCA. However, the systolic velocity returned to values similar to those of the control group with the accumulation of nights with sleep deprivation.
Conclusions
Our study indicates that those who do not get sufficient sleep, display sudden alterations in their cardiovascular parameters, which are consistent with an increased risk of developing coronary heart disease, myocardial infarction, stroke, and hypertension.
General anesthesia, as a commonly used medical intervention, has been widely applied during surgical procedures to ensure rapid loss of consciousness and pain relief for patients. However, recent research suggests that general anesthesia may be associated with the occurrence of perioperative neurocognitive disorder (PND). PND is characterized by a decline in cognitive function after surgery, including impairments in attention, memory, learning, and executive functions. With the increasing trend of population aging, the burden of PND on patients and society’s health and economy is becoming more evident. Currently, the clinical consensus tends to believe that peripheral inflammation is involved in the pathogenesis of PND, providing strong support for further investigating the mechanisms and prevention of PND.
Although studies have shown that light affects sleep in polar populations, the sample size of most studies is small. This meta‐analysis provides the first systematic review of the effects of summer glare, spring and fall moderate daylight, and artificial lighting on general sleep problems (sleep duration, efficiency, and delay). This analysis included 18 studies involving 986 participants. We calculated the random effect size via an evidence‐based meta‐analysis that analysed the effect of bright/auxiliary light on sleep and the effect of three different types of light on sleep compared with conventional light. There was no significant correlation between specific light types and sleep duration. Intense summer light has a negative effect on sleep time and efficiency. Moderate, natural light in spring and autumn effectively delayed sleep but could not improve sleep efficiency. For artificial fill light, neither blue light nor enhanced white light has been found to have a significant effect. In summary, summer light has a detrimental effect on sleep in polar populations, and moderate natural light may be superior to conventional light. However, specific strategies to improve sleep and artificial lighting in polar populations must be explored further.
Objective: Shoulder pain, a common musculoskeletal issue, is most prevalent in patients aged 50-59. It can cause sleep problems, reducing sleep quality. We aimed to explore the relationship between sleep quality, pain, and disability in patients with shoulder pain, despite limited literature on this issue. Material-Method: Study involved 91 patients aged 18-80 with persistent shoulder pain sought out at a physical medicine and rehabilitation outpatient clinic. Factors such as age, gender, education, symptom duration, body mass index (BMI), occupation, and pain severity were recorded. Severity of pain was assessed using the visual analogue scale (VAS), pain and disability using the Shoulder Pain and Disability Index (SPADI), and sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Results: Average age was 54.9. 63% of patients were female and 28% were male. 14% of them had heavy work above shoulder level. A positive correlation was detected between PSQI and VAS and SPADI (p value 0.004 and 0.003, respectively). No significant relationship was found between PSQI and BMI and symptom duration (p value 0.464 and 0.718, respectively). While there was a significant difference in SPADI values between two groups with and without heavy work above the shoulder level, no significant difference was detected in PSQI values (p value 0.021 and 0.36, respectively). Conclusion: We found that the patient's VAS and SPADI values and sleep quality were negatively related to shoulder pain. Sleep disturbance due to pain at night can also affect daytime disability. Pain and sleep quality disorders can enter a vicious circle.
Background
Sleep has an essential role in restoring brain activity and balancing physiological, immune, and metabolic factors in the body. Individuals, after being infected with COVID-19, have been reported to have quite a lot of symptoms related to sleep disorders, so we conducted this study to evaluate sleep disorders in patients with COVID-19.
Methods
This study involved a cross-sectional design; 547 patients hospitalised due to COVID-19 and aged 18 years and above were included. The study used the questionnaire designed by the Vietnam Society of Sleep Medicine (VSSM). Collected data were statistically analyzed and results have been obtained using SPSS software version 22.0.
Results
Nightmares have been found to be increased by 10.1%, sleep quality decreased by 51.2%, and insomnia increased by 19%, compared to pre-infection. There were 24% of participants with daytime sleepiness syndrome, 23% with symptoms of memory impairment, 17% with unexplained anxiety and frustration, and 10% with loud snoring. In addition, the manifestations of sleep disorders also became more and more severe than before the infection. 68.4% of subjects were not satisfied with their current sleeping, 29.1% had sleep difficulties, including maintaining sleep, and 19.4% had trouble falling asleep.
Conclusion
Sleep disturbance is a critical and common medical condition in COVID-19 patients. It is necessary to have appropriate treatment measures for insomnia in COVID-19 patients to help improve their health status and avoid post-COVID-19 sequelae.
Globally, sleep deprivation is a concerning health issue associated with an increased risk of cardiovascular diseases (CVDs). The present study aimed to explore the association between short-term sleep and the risk of CVDs, taking into consideration sex and age groups. A comprehensive review was conducted by assembling cohort studies that are available in the PubMed, Cochrane Library, and Embase databases. Individuals with ≤5 or ≤6 h of sleep per day were considered as sleep-deprived subjects. To minimize potential bias, two reviewers thoroughly evaluated the selected articles. Relevant data were extracted, and pooled odds ratios (ORs) or relative risks (RRs) were calculated using a random-effects model. In total, 18 cohort studies involving adult subjects were included in the present analysis. The pooled results strongly indicated that sleep deprivation was associated with a greater risk of CVDs [RR: 1.09, 95% confidence interval (CI): 1.02-1.16, P=0.009]. However, when the pooled analysis was stratified by sex and age, the following results were observed: short-term sleep women (RR: 1.06, 95% CI: 0.96-1.17, P=0.27), short-term sleep men (RR: 1.07, 95% CI: 0.97-1.17, P=0.17); ≥18 years-old sleep-deprived population (RR: 1.09, 95% CI: 1.00-1.17, P=0.04), ≥40 years-old sleep-deprived population (RR: 1.09, 95% CI: 0.98-1.22, P=0.11), and subjects with co-existing diseases, such as diabetes and hyperlipidemia (RR: 1.06, 95% CI: 0.94-1.20, P=0.32). In conclusion, short-term sleep is associated with the increased risk of CVDs. Among subjects who were aged ≥18 years-old, there was a strong association with the development of CVDs compared with those who were aged ≥40 years-old. Furthermore, men were at a higher risk of CVDs than women. Adequate sleep (7-8 h per day) may play a role in improving cardiac health. The results of the present study may provide valuable support for further research in public health, highlighting the correlation between sleep deprivation and the risk of CVDs.
Background: The modern medical community now recognises Amavata as a condition that can lead to Rheumatoid Arthritis (RA) due to a combination of genetic predisposition, poor dietary habits, altered lifestyle, disturbed sleep, disturbed psychological condition, etc. Amavata's origins are said to be two thousand years old, but there is no rigid evidence to support this. Aim: To evaluate the association of family history, different dietary patterns and lifestyle related risk factors such as Vyayama, improper bowel movements, disturbed/irregular sleep patterns, psychological stress, etc., in the pathology of Amavata (~RA). Materials and Methods: A matched case-control study was conducted from 18 April 2018 to 09 January 2020, containing 150 cases (patients of Amavata), and 150 controls (healthy volunteers), matching in age (between 18-50 years), and both the sexes (1:1 ratio) selected from Jamnagar district. After receiving written informed permission, data were obtained using CRF (Case Record Form). An open-ended questionnaire through the one-to-one interview was used to obtain data on eating habits, psychological and emotional circumstances previous to sickness, lifestyle features such as sleep, Vyayama (physical activity), and bowel patterns. Chi-square tests and Odds Ratios (OR) were computed. Results: The statistical analysis revealed that positive family history (χ 2 = 63.021, p<0.001), Avyayama (lack of physical activity) (OR = 7.43, χ 2 = 79.95, p<0.001), Diwaswapna (day time sleep) (OR = 12.86, χ 2 = 93.048, p<0.001), disturbed night sleep (OR = 44.25, χ 2 = 159.61, p<0.001), constipation (OR = 85.17, χ 2 = 144.10, p<0.001), Atishrama (occupational stress)(OR = 22.86, χ 2 = 96.989, p<0.001), disturbed psychological status (p<0.001) and faulty dietary patterns (p<0.001) were found to have statistically significant association with Amavata (~RA). Conclusion: Strong positive associations were found between positive family history, Avyayama (lack of physical activity), Diwaswapna (daytime sleep), disturbed night sleep, constipation, disturbed psychological status, Atishrama (occupational stress), and faulty dietary patterns (Adhyashana, Vishamashana, Viruddhashana) with Amavata which are statistically significant and they can be considered as the potential risk factors for the incidence of Amavata (~RA).
Background
Surgical weight loss procedures like vertical sleeve gastrectomy (SG) are sufficient in resolving obesity comorbidities and are touted to reduce the burden of pro-inflammatory cytokines and augment the release of anti-inflammatory cytokines. Recent reports suggest a reduced improvement in weight resolution after SG in Black Americans (BA) versus White Americans (WA). The goal of this study was to determine if differences in immunoglobulin levels and general markers of inflammation after SG in Black Americans (BA) and White Americans (WA) may contribute to this differential resolution.
Methods
Personal information, anthropometric data, and plasma samples were collected from 58 participants (24 BA and 34 WA) before and 6 weeks after SG for the measurement of immunoglobulin A (IgA), IgG, IgM, C-reactive protein (CRP), and transforming growth factor (TGFβ). Logistic regression analysis was used to determine the relationship of measures of body size and weight and inflammatory markers.
Results
Both IgG and CRP were significantly elevated in BA in comparison to WA prior to weight loss. Collectively, IgG, TGFβ, and CRP were all significantly reduced at six weeks following SG. CRP levels in BA were reduced to a similar extent as WA, but IgG levels were more dramatically reduced in BA than WA despite the overall higher starting concentration. No change was observed in IgA and IgM.
Conclusions
These data suggest that SG improves markers of immune function in both BA and WA. More diverse markers of immune health should be studied in future work.
Objectives: Neck pain is extremely common and represents a substantial economic burden to our society. We aimed to investigate risk factors for nondisabling and disabling neck pain in a large cohort of Ital-ian adolescents with a cross-sectional study. Design: Six thousand two hundred eighty-one students (14-19 yrs old) answered an online questionnaire, investigating the following: an-thropometric data, lifestyle-related items, neck pain frequency and intensity , need for medical examination, and several risk factors. Students who had to give up social activities because of neck complaints constituted the disabling neck pain group. Results: Our findings revealed that sex, age, sports practice, hours of sleep, and family history were risk factors (P < 0.001) for neck pain in our cohort. Moreover, disabling neck pain group experienced neck pain more frequently (P < 0.001) and with higher levels of pain (P < 0.001) compared with the nondisabling group. The number of hours of sleep was the only risk factor that showed a trend to differ comparing the disabling neck pain group with the nondisabling neck pain one (P = 0.057). Conclusions: Different risk factors for neck pain were detected in a very large cohort of adolescents. This study may pave the way for future prospective studies and for the development of preventive strategies for neck pain in adolescents.
Background:
Previous studies documented a narrow scope of knowledge about the negative mental health status during the lockdown following the COVID-19 pandemic, especially in Arab countries.
Aim:
We aimed to assess the association between negative mental health status and the COVID-19 pandemic and determine the different factors affecting mental health among the general population of seven Arab countries.
Methods:
This study is a multinational cross-sectional questionnaire-based survey conducted online from June 11, 2020 to June 25, 2020. The depression, anxiety, and stress Scale 21 Items (DASS-21) and the Event scale-Revised Arabic version (IES-R-13) scales were used. Multiple linear regressions were performed to study the association between the scales' total scores with COVID-19 and demographic characteristics.
Results:
A total of 28,843 participants from seven Arab countries were included. During the COVID-19 pandemic, the prevalence of mental health disorders has significantly increased. A total of 19006 participants (66%) were affected by variable degrees of depression, 13,688 (47%) had anxiety, and 14,374 (50%) had stress ranging from mild to severe. Higher levels were associated with other factors, such as lower age, female gender, chronic disease, unemployed, fear of getting infected, and a history of psychiatric disorders.
Conclusion:
Our study findings show an increased incidence of mental disorders during the pandemic. This is expected to play a crucial role in guiding a psychological support strategy provided by healthcare systems to the general public during pandemics.
Circadian rhythms are a series of endogenous autonomous oscillators that are generated by the molecular circadian clock which coordinates and synchronizes internal time with the external environment in a 24-h daily cycle (that can also be shorter or longer than 24 h). Besides daily rhythms, there exist as well other biological rhythms that have different time scales, including seasonal and annual rhythms. Circadian and other biological rhythms deeply permeate human life, at any level, spanning from the molecular, subcellular, cellular, tissue, and organismal level to environmental exposures, and behavioral lifestyles. Humans are immersed in what has been called the “circadian landscape,“ with circadian rhythms being highly pervasive and ubiquitous, and affecting every ecosystem on the planet, from plants to insects, fishes, birds, mammals, and other animals. Anthropogenic behaviors have been producing a cascading and compounding series of effects, including detrimental impacts on human health. However, the effects of climate change on sleep have been relatively overlooked. In the present narrative review paper, we wanted to offer a way to re-read/re-think sleep medicine from a planetary health perspective. Climate change, through a complex series of either direct or indirect mechanisms, including (i) pollution- and poor air quality-induced oxygen saturation variability/hypoxia, (ii) changes in light conditions and increases in the nighttime, (iii) fluctuating temperatures, warmer values, and heat due to extreme weather, and (iv) psychological distress imposed by disasters (like floods, wildfires, droughts, hurricanes, and infectious outbreaks by emerging and reemerging pathogens) may contribute to inducing mismatches between internal time and external environment, and disrupting sleep, causing poor sleep quantity and quality and sleep disorders, such as insomnia, and sleep-related breathing issues, among others. Climate change will generate relevant costs and impact more vulnerable populations in underserved areas, thus widening already existing global geographic, age-, sex-, and gender-related inequalities.
Sleep restriction and fragmentation is commonly observed in the ICU related to excessive light, noise, patient care interventions and critical illness itself. Abnormalities in sleep architecture and duration are associated with neurocognitive impairments and adverse patient outcomes. Sleep deprivation is also known to impair glucose metabolism and immune function, which could contribute to ICU morbidity. Circadian rhythm disturbances frequently arise in ICU patients related to non-standard environmental cues that may contribute to the development of delirium. Poor quality sleep in the ICU may have important clinical consequences including impeding ventilator weaning, effects on other organ systems, and impacts on mood. Together, these have implications for recovery from critical illness both within the hospital and afterward. While a growing body of research has begun to illuminate the relationship between sleep disruption and outcomes in the ICU population, much can be inferred about this connection from studies of other populations, including hospitalized patients and outpatients subject to acute sleep deprivation.KeywordsCircadian disruptionCritical illnessDeliriumGlucose metabolismICU outcomesImmune functionInflammationNeurocognitive functionPost-Intensive Care Unit Syndrome (PICS)Sleep disruption
There is broad variety in the manner in which neck pain is defined. While examination when providing details for neck pain there are five key points which apparently represented: 1. the origin of issue and information; 2. the situation or testing outline; 3. the neck pain seriousness, also the outcomes; 4. the neck pain extent; 5. the example after some moments. Other evidence showed there is lacking in amount and quality of sleep results in musculoskeletal displacement by patho-physiologically. The pain occurrence and the progression include many environmental and social causes which is widespread. Objective: The purpose of this study was to find the association of decreased daily physical activities, disturbed sleep pattern with cervical pain among young adults. Methods: A cross-sectional survey was conducted on 90 persons presenting with cervical pain. Data was collected from students of University of Lahore. Non-probability Convenient Sampling Technique was used. Northwick Park Neck Pain Questionnaire and The Sleep Revolution Sleep Quality Questionnaire by Arianna Huffington were used to collect data. Results: The total population was 90, which includes 33 males and 57 females with percentage 36.7% and 63.3% respectively. On pain scale to assess the cervical pain there were 43 (47.8%) persons with Mild pain, 37 (41.1%) having Moderate pain and 10 (11.1%) with severe pain. There were 58 (64.4%) persons are physically active even after cervical pain and 32(35.6%) physically not active. There were 3(3.3%) who have severed sleep problems, 16(17.8%) were with some sleep problems, 43(47.8%) having good sleep and 28(31.1%) sleep is in great shape. In this Study there was no association occurs between daily activities, sleep disturbance with cervical pain in overall results. Conclusion: In this study overall, there was no association occurred in persons who were having any sort of cervical pain with daily physical activities and sleep patterns disturbance. As some of the individual activities like daily working, house hold activities, driving is affected in some of the cases with cervical pain.
Sleep loss has negative impacts on quality of life, mood, cognitive function and heath. Insomnia or difficulty sleeping is also a prevalent issue, affecting up to 35% of the population at some point in their lives. Insomnia is linked to poor mood, increased use of health care resources, and decreased quality of life as well as possible links to cardiovascular risk factors and disease. Studies have shown an increase in cortisol levels, decreased immunity, and increased markers of sympathetic activity in sleep-deprived healthy subjects and those with chronic insomnia. The literature also shows that subjective complaints consistent with chronic insomnia and shortened sleep time, both independently and in combination, can be associated with the development of diabetes, hypertension, and cardiovascular disease. In this article, we will explore the relationship and strength of association between insufficient sleep and insomnia with these health conditions.
Background:
Many cross-sectional studies have examined the predictors of neck pain among adolescents and working-age populations, but there are limited studies included undergraduate students.
Objective:
To investigate the predictors of neck disability among undergraduate students.
Methods:
A cross-sectional study using a self-administered online survey. Students completed the survey that included socio-demographic factors, academic-related factors, health and lifestyle factors, and standardized questionnaires including Neck Disability Index (NDI), 12-Item Short-Form Health Survey (SF-12), Depression Anxiety Stress Scales (DASS-21), and Pittsburgh Sleep Quality Index (PSQI). Students who reported an NDI score higher than 15 were considered as having a neck disability. A multivariable logistic regression model was used to identify the significant predictors of neck disability.
Results:
Of all students (n = 1292), 20.8% reported neck disability. Among all possible predictors, students' major satisfaction (OR 1.46 [95% CI 1.06-2.01]; p = 0.019), DASS-21 anxiety score (OR 1.06 [95% CI 1.03-1.09]; p < 0.001), SF-12 total score (OR 0.89 [95% CI 0.86-92]; p < 0.001), and PSQI score (OR 1.21 [95% CI 1.15-1.28]; p < 0.001) were the only significant predictors of neck disability.
Conclusions:
Increased levels of academic stressors and anxiety, and decreased levels of quality of life and sleep quality are associated with increased neck disability among undergraduate students.
Background: Post-traumatic stress disorder (PTSD) metacognitive model is considered a model with good power. There are not enough data that this model is appropriate to combat veterans with chronic PTSD. Objectives: This study aimed to investigate the association between metacognition components, including metacognitive beliefs and attitudes, meta-worry, rumination, and cognitive-attentional syndrome (CAS), in Iranian combat veterans with PTSD. Methods: The population of this study included all combat veterans referred to the rehabilitating center of Sari, Mazandaran province in 2016. After a clinical interview by a clinical psychologist, the veterans were divided into three groups (PTSD, non-PTSD, and non-traumatized). These three groups matched in age, gender, and socio-economic status. Exclusion criteria for three groups were as follows: Those who had a significant psychiatric disorder that has been active during the research plan. Moreover, data gathering instrument used in the current research was Metacognition Questionnaire [including Metacognitive Questionnaire (MCQ), Ruminative Responses Scale (RRS), Cognitive-Attentional Syndrome Scale (CAS-1), Impact of Event Scale-Revised (IES-R), and Meta-worry Questionnaire (MWQ)]. One-way variance analysis was used to compare groups in terms of metacognition, meta-worry, rumination, and CAS. Conclusions: Consistent with the metacognitive model of PTSD, metacognition components, ruminative responses, cognitive-attentional syndrome, and meta-worry have significant differences with non-PTSD and non-traumatized. It appears that meta-cognitive components are more disruptive in PTSD patients than other control groups. This finding could be integrated into the metacognition theory.
Risk factors for low back pain (LBP) flares have been considered with respect to self-reported measures. This case-crossover study aimed to investigate whether: i) objective measures of physical activity and sleep were associated with risk of experiencing LBP flares; and ii) these associations differed for flares defined as pain 2 or more points greater than average pain over the period using an 11-point Numerical Rating Scale (NRS; 0-no pain, 10-worst pain imaginable)(pain-defined flare: PDF) and flares identified by participants according to a broader definition that considered emotions/coping (self-reported flare: SRF). We included 126 participants who had experienced LBP for >3 months. Physical activity and sleep were monitored for 28 days using wearable sensors. Occurrence of flares (PDF/SRF) were assessed daily using a smartphone application. Data on exposure to risk factors one, two and three days preceding PDF/SRF were compared to non-flare control periods. Conditional logistic regression determined association between each factor and flares. Data show that day-to-day variation in physical activity and in-bed time are associated with risk of LBP flares, but associations differ depending on how flare is defined. Longer in-bed time increased the risk of PDF, but not SRF. Although physical activity was not associated with risk of PDF, greater sedentary behaviour increased risk of SRF and being more physically active decreased risk for SRF. These results highlight the potential role of targeting sleep and physical activity in interventions to prevent LBP flares, and indicate that risk factors differ depending on how LBP flares are defined.
A reduction in immune function has been found in patients with a major depressive disorder and in persons undergoing severe life stress. This study investigated the association between increased sympathetic nervous system activity and reduced natural killer (NK) cytotoxicity in depression and Alzheimer caregiver stress. NK activity and plasma concentrations of epinephrine, norepinephrine, and neuropeptide Y were measured in depressed patients (n = 19) and age- and gender-matched controls (n = 19), and in Alzheimer spousal caregivers (n = 48) and matched noncaregiver controls (n = 17). Plasma levels of neuropeptide Y, but not circulating basal levels of catecholamines, were significantly (P less than 0.01) elevated in the depressed patients and in the caregivers compared with respective controls. NK activity was significantly (P less than 0.001) lower in the depressed patients than in their controls, but not different between the caregivers and the noncaregiver controls. Circulating concentrations of neuropeptide Y, but not catecholamines, were inversely correlated (r = -0.31, P less than 0.001) with NK activity. In addition, multiple regression analyses demonstrated that the significant (P less than 0.01) association between neuropeptide Y and natural cytotoxicity was independent of the relative contribution of age and basal and dynamic levels of epinephrine and norepinephrine. These findings suggest that increased sympathetic nervous system activity and the release of neuropeptide Y may be associated with the modulation of NK cytotoxicity.
Interleukin-6 (IL6) induces acute phase protein production and is hypothesized to mediate systemic and central effects of IL1. To determine whether IL6 possesses somnogenic properties, rabbits were injected intracerebroventricularly with IL6; sleep-wake activity was determined and brain temperatures recorded for 6 hr. IL6 induced fever in a dose-related manner with no effect on sleep-wake activity. IL6, therefore, is the first cytokine reported to elicit fever without promoting sleep. We conclude that the somnogenic action of IL1 is not mediated through IL6.
This paper reviews the relationship of aspects of the immune system to the sleep-wake system in animals and humans. In addition to the influence of certain cytokines such as interleukin-1 (IL-1) on the sleeping-waking brain, circadian measures of plasma IL-1 and peripheral immune cellular functions, for example, natural killer cell activities and cortisol are related to the sleep-wake system in humans. Changes in the circadian patterns of immune functions over the menstrual cycle are associated with the amount of progesterone and slow wave sleep. The harmonious inter-relationship of the circadian pattern of the immune, endocrine and sleep-wake systems may be important in the cause and functions of sleep.
The hypothesis that sleep deprivation depresses immune function was tested in 20 adults, selected on the basis of their normal blood chemistry, monitored in a laboratory for 7 d, and kept awake for 64 h. At 2200 h each day measurements were taken of total leukocytes (WBC), monocytes, granulocytes, lymphocytes, eosinophils, erythrocytes (RBC), B and T lymphocyte subsets, activated T cells, and natural killer (NK) subpopulations (CD56/CD8 dual-positive cells, CD16-positive cells, CD57-positive cells). Functional tests included NK cytotoxicity, lymphocyte stimulation with mitogens, and DNA analysis of cell cycle. Sleep loss was associated with leukocytosis and increased NK cell activity. At the maximum sleep deprivation, increases were observed in counts of WBC, granulocytes, monocytes, NK activity, and the proportion of lymphocytes in the S phase of the cell cycle. Changes in monocyte counts correlated with changes in other immune parameters. Counts of CD4, CD16, CD56, and CD57 lymphocytes declined after one night without sleep, whereas CD56 and CD57 counts increased after two nights. No changes were observed in other lymphocyte counts, in proliferative responses to mitogens, or in plasma levels of cortisol or adrenocorticotropin hormone. The physiologic leukocytosis and NK activity increases during deprivation were eliminated by recovery sleep in a manner parallel to neurobehavioral function, suggesting that the immune alterations may be associated with biological pressure for sleep.
Prolonged and severe sleep deprivation is associated with alterations of natural and cellular immune function. To determine whether alterations of immune function also occur after even a modest loss of sleep, the effects of early-night partial sleep deprivation on circulating numbers of white blood cells, natural killer (NK) cell number and cytotoxicity, lymphokine-activated killer (LAK) cell number and activity, and stimulated interleukin-2 (IL-2) production were studied in 42 medically and psychiatrically healthy male volunteers. After a night of sleep deprivation between 10 P.M. and 3 A.M., a reduction of natural immune responses as measured by NK cell activity, NK activity per number of NK cells, LAK activity, and LAK activity per number of LAK precursors (CD16,56, CD25) was found. In addition, concanavalin A-stimulated IL-2 production was suppressed after sleep deprivation due to changes in both adherent and nonadherent cell populations. After a night of recovery sleep, NK activity returned to baseline levels and IL-2 production remained suppressed. These data implicate sleep in the modulation of immunity and demonstrate that even a modest disturbance of sleep produces a reduction of natural immune responses and T cell cytokine production.
The role of nocturnal sleep for normal immune regulation and its relation to circadian rhythm was examined in 10 men participating in two 51-h sessions. One session included two regular wake-sleep cycles; the other included a night of sustained wakefulness followed by a night of recovery sleep. Blood was collected every 3 h to determine PBMC counts, including the enumeration of monocytes, NK cells, and lymphocyte subsets (CD19+, CD3+, CD4+, CD8+, HLA-DR+). Production of IL-1beta, TNF-alpha, IL-2, and IFN-gamma was determined after stimulation of whole blood samples with LPS and PHA, respectively. Concentrations of IL-6 and cortisol were assessed in plasma. Enumeration of cells indicated significant circadian rhythms for all PBMC subsets under conditions of sustained wakefulness. Compared with sustained wakefulness, nocturnal sleep acutely reduced the numbers of monocytes, NK cells, and counts of all lymphocyte subsets. However, in the afternoon and evening of the day following sleep, counts of NK cells and lymphocytes were significantly higher than after nocturnal wakefulness, indicating that effects of sleep interacted with those of the circadian pacemaker. Sleep markedly enhanced production of IL-2 by T cells (CD3+) but did not influence production of IL-1beta and TNF-alpha, or IL-6 concentrations. Effects of sleep were not mediated by changes in cortisol. The decrease in monocytes, NK cells, and lymphocytes, together with an increased production of IL-2 during sleep, may serve to support ongoing immune defense in extravascular lymphoid tissue during a time of diminished acute Ag challenge.
This paper shows that melatonin is able to activate human Th1 lymphocytes by increasing the production of IL-2 and IFN-gamma in vitro. Th2 cells appear not to be affected by melatonin, since IL-4, which is mostly produced by Th2 cells, is not modified by the hormone. Melatonin also enhances IL-6 production by PBMCs. The activation by melatonin of IL-6 production is apparently related to the presence of monocytes, rather than to Th2 cells, in the cell preparation, since PBMCs depleted of monocytes (CD14+ cells) were not activated. Activation of PBMCs by melatonin was dependent on the dose and, measured by cytokine production, was observed only when cells were either not activated or only slightly activated by low concentrations of PHA, or when cell activation was achieved by incubating the cells with previously irradiated cells. Using a different approach to identify what type of cells among the PBMC subsets was activated by melatonin, the expression of CD69, a marker of cell activation, was studied. Melatonin increased the percentage of cells expressing the CD69 Ag in CD4+ but not in CD8+ cells. We have also achieved enhanced production of IL-2 and IL-6 using CGP 52608, a specific ligand of the putative nuclear melatonin receptor RZR/ROR, raising the possibility of direct effects of melatonin on gene regulation in both Th1 cells and monocytes. The results suggest that melatonin may be involved in the regulation of human immune functions by modulating the activity of Th1 cells and monocytes via nuclear receptor-mediated transcriptional control.
Interleukin-6, an inflammatory cytokine, is characterized by pleiotropy and redundancy of action. Apart from its hematologic, immune, and hepatic effects, it has many endocrine and metabolic actions. Specifically, it is a potent stimulator of the hypothalamic-pituitary-adrenal axis and is under the tonic negative control of glucocorticoids. It acutely stimulates the secretion of growth hormone, inhibits thyroid-stimulating hormone secretion, and decreases serum lipid concentrations. Furthermore, it is secreted during stress and is positively controlled by catecholamines. Administration of interleukin-6 results in fever, anorexia, and fatigue. Elevated levels of circulating interleukin-6 have been seen in the steroid withdrawal syndrome and in the severe inflammatory, infectious, and traumatic states potentially associated with the inappropriate secretion of vasopressin. Levels of circulating interleukin-6 are also elevated in several inflammatory diseases, such as rheumatoid arthritis. Interleukin-6 is negatively controlled by estrogens and androgens, and it plays a central role in the pathogenesis of the osteoporosis seen in conditions characterized by increased bone resorption, such as sex-steroid deficiency and hyperparathyroidism. Overproduction of interleukin-6 may contribute to illness during aging and chronic stress. Finally, administration of recombinant human interleukin-6 may serve as a stimulation test for the integrity of the hypothalamic-pituitary-adrenal axis.
We have previously described a temporal relationship between plasma cortisol pulses and slow-wave sleep and, more recently, an inverse significant cross-correlation between cortisol secretory rates and delta wave activity of the sleep electroencephalogram (EEG). The aim of this study was to observe ACTH, cortisol, and sleep delta wave activity variations throughout 24 h to get a better insight into their initiating mechanisms. Two groups of 10 subjects participated in a 24-h study, one group with a night sleep (2300-0700) and the other with a day sleep (0700-1500). Cortisol secretory rates were calculated by a deconvolution procedure from plasma levels measured at 10-min intervals. Delta wave activity was computed during sleep by spectral analysis of the sleep EEG. When delta waves and cortisol were present at the same time at the end of the night sleep as well as during the daytime sleep, they were negatively correlated, cortisol changes preceding variations in delta wave activity by approximately 10 min. Increases in delta wave activity occurred in the absence of cortisol pulses, as observed at the beginning of the night. Cortisol pulses occurred without any concomitant variations of sleep delta wave activity, as observed during wakefulness and intrasleep awakenings. In no case did delta wave activity increase together with an increase in cortisol secretory rates. In conclusion, cortisol secretion and delta wave activity have independent generators. They can oscillate independently from each other, but when they are present at the same time, they are oscillating in phase opposition.
The aging process is associated with a significant reduction in circulating GH and insulin-like growth factor I (IGF-I) levels. During this period, immune function also declines. Rodent data suggest that treatment with recombinant human GH (rhGH) or rhIGF-I enhances immune function in normal adult mice. To determine whether rhGH and/or rhIGF-I treatment could improve immune function in aged female rhesus monkeys, we administered rhIGF-I (120 micrograms/kg x day), rhGH (100 micrograms/kg x day), a combination of therapies, or excipient alone by sc infusion using Alzet pumps over a 7-week period. At 28 days, the pumps were replaced, and the animals were bled and immunized with tetanus toxoid. At the end of the 7-week period, the animals were killed. rhGH and rhIGF-I increased serum GH and IGF-I levels, respectively; rhGH and rhIGF-I in combination induced the highest serum IGF-I levels (906 +/- 261 ng/ml vs. control, 185 +/- 36 ng/ml at death). rhGH and rhIGF-I also increased IGFBP-3 levels. rhGH infusion r...
The past two decades have provided a vast array of information about growth hormone (GH) at the molecular, cellular, and organismic level. GH is an anterior pituitary, peptide hormone that binds to cell surface receptor via a two-step mechanism. The resulting change in receptor structure increases the affinity and activation of JAK-2, which phosphorylates itself and the receptor, forming high affinity binding sites for signaling proteins. The recruitment of numerous signaling molecules leads to the activation of multiple pathways that control gene transcription and metabolism. GH elicits its effects on a wide variety of tissues, including cell of the immune system that also produce small amounts of GH. Different cell types of the immune system respond to GH in a variety of functional assays. Models of GH defficiency are not usually associated with clinically relevant immonudeficiency that may in part be explained by cytokine redundancies. The theraphuetic use of GH, however, appears to be for the most part beneficial and needs to be studied further.
The central thesis of this essay is that the cytokine network in brain is a key element in the humoral regulation of sleep responses to infection and in the physiological regulation of sleep. We hypothesize that many cytokines, their cellular receptors, soluble receptors, and endogenous antagonists are involved in physiological sleep regulation. The expressions of some cytokines are greatly amplified by microbial challenge. This excess cytokine production during infection induces sleep responses. The excessive sleep and wakefulness that occur at different times during the course of the infectious process result from dynamic changes in various cytokines that occur during the host's response to infectious challenge. Removal of any one somnogenic cytokine inhibits normal sleep, alters the cytokine network by changing the cytokine mix, but does not completely disrupt sleep due to the redundant nature of the cytokine network. The cytokine network operates in a paracrine/autocrine fashion and is responsive to neuronal use. Finally, cytokines elicit their somnogenic actions via endocrine and neurotransmitter systems as well as having direct effects on neurons and glia. Evidence in support of these postulates is reviewed in this essay.
Systemic administration of growth hormone-releasing hormone (GHRH) has been found to improve human sleep in previous studies. Here we examined effects of GHRH on endocrine function and sleep after intranasal administration, a method which based on previous studies appears to enable a direct effect of peptides on brain function. Also, it was hypothesized that elderly humans displaying deficient GH release and sleep, benefit from GHRH administration more than young subjects. A study was performed according to a double-blind cross-over design. Each of 12 young and 11 old healthy men were intranasally administered with 300 μg GHRH (vs. placebo) 30 min before bedtime at 23:00 h. Sleep was recorded polysomnographically until 07:00 h and blood was collected in 15 min intervals for determination of cortisol and GH. Apart from the well-known age-related changes of hormonal secretion and sleep, intranasal GHRH reduced cortisol nadir concentrations in the beginning of sleep (P<0.05), and also reduced the sleep-induced elevation in GH concentrations during early sleep. Moreover, results indicated that after intranasal administration GHRH increased rapid-eye-movement (REM) sleep and slow wave sleep (SWS), with this influence concentrating on the second half of sleep time. Effects of GHRH did not depend on the subject’s age. We conclude that there is a coordinate influence of intranasal GHRH on the central nervous regulation of sleep processes and of hypothalamic–hypophysiotropic secretory activity in both young and elderly men. The effects may mimic the dual neuronal and endocrine function of hypothalamic GHRH activity.
We examined the association between 6-sulphatoxymelatonin (6-SMT) excretion and sleep in 68 volunteers 60-79 years of age who complained of insomnia or depression. An Actillume wrist monitor was worn for 5-7 consecutive days and nights in home-living conditions. Activity was used to estimate total sleep time (TST) and wake after sleep onset (WASO). Throughout two 24 hr periods, urine was collected approximately every 2 hr during the day and after any voidings during the sleep period. During the next week, subjects spent 5 nights and 4 days in the laboratory. Sleep was measured and scored with standard polysomnographic techniques. Urine was collected, as for home recording, on days 1 and 4. Urinary concentrations of 6-SMT were assayed. Cosine-fitting of urine data across both days at home and both laboratory collections established the mesors and amplitudes of 24 hr 6-SMT excretion rhythms, but neither was significantly correlated with sleep. Mean and peak 6-SMT excretion during the sleep period was also determined. Significant correlations were found between mean 6-SMT during the laboratory sleep period and TST and WASO. However, these associations were not independent of circadian timing: sleep was better when sleep occurred near the circadian acrophase of 6-SMT excretion. These data indicate that low melatonin production may not be an important factor in insomnia among the elderly.
"Department of Physiology." Thesis (M.S)--Southern Illinois University at Carbondale, 1997. Vita. Includes bibliographical references (leaves 60-68).
The relation between the sympathetic nervous system and the immune system has not been fully defined. Recent investigations have suggested an adrenergically driven efflux of specific beta 2-receptor-rich lymphocyte subsets into the circulation with either exercise or infusion of exogenous catecholamines.
To determine whether acute sympathetic stimulation mediates immunoregulatory cell traffic and function via a beta 2-receptor mechanism, we exercised 20 healthy volunteers before and after 1 week of treatment with either the nonselective beta-antagonist propranolol or the beta 1-selective antagonist metoprolol. Before treatment, exhaustive exercise according to the Bruce protocol led to a marked lymphocytosis. Tsuppressor/cytotoxic (Ts/c) and natural killer cells, subtypes with the largest density of beta-receptors, showed the most pronounced increases after exercise, with less impressive elevations in T(helper) and B cells. With respect to function, exhaustive exercise led to a decrease in concanavalin A-stimulated IL-2 receptor expression and [3H]thymidine incorporation while enhancing natural killer cell activity. One week of propranolol therapy blunted the exercise-induced increases in circulating Ts/c and natural killer subpopulations as well as the previously observed alterations in cellular immune function. Treatment with the beta 1-selective antagonist metoprolol, however, did not impair the influence of exercise on any of the above parameters.
Acute sympathetic stimulation by exhaustive exercise leads to selective release of immunoregulatory cells into the circulation with subsequent alterations in cellular immune function, either secondary to subset changes or as a result of direct catecholamine effects on function. These changes are attenuated by propranolol but not metoprolol, suggesting a beta 2-mediated mechanism.
Exogenously administered tumor necrosis factor-alpha (TNF-alpha) elicits several symptoms of generalized infections such as fever, increased sleep, and anorexia. The aim of the present work was to localize these effects of TNF-alpha to specific amino acid sequences of the parent molecule by characterizing the in vivo and in vitro activities of several synthetic TNF-alpha fragments. Intracerebroventricular injection of TNF-alpha elicited dose-dependent fevers and increases in non-rapid-eye-movement sleep (NREMS) in rabbits. Four fragments also promoted NREMS and five elicited monophasic fevers. All of the somnogenic fragments share the amino acid sequence 31-36. In rats, TNF-alpha and one of the fragments [TNF-alpha-(69-100)] suppressed 12-h food intake. Furthermore, TNF-alpha increased the expression of the intercellular adhesion molecule-1 and enhanced interferon-gamma-induced HLA-DR expression in human glioblastoma cell line. In contrast, none of the fragments possessed these in vitro activities. Our in vivo results support the concept that there are biologically active regions in the TNF-alpha molecule.
We reviewed the literature on sleep in psychiatric disorders and evaluated the data by meta-analysis, a statistical method designed to combine data from different studies. A total of 177 studies with data from 7151 patients and controls were reviewed. Most psychiatric groups showed significantly reduced sleep efficiency and total sleep time, accounted for by decrements in non-rapid eye movement sleep. Rapid eye movement sleep time was relatively preserved in all groups, and percentage of rapid eye movement sleep was increased in affective disorders. Reduction in rapid eye movement sleep latency was seen in affective disorders but occurred in other categories as well. Although no single sleep variable appeared to have absolute specificity for any particular psychiatric disorder, patterns of sleep disturbances associated with categories of psychiatric illnesses were observed. Overall, findings for patients with affective disorders differed most frequently and significantly from those for normal controls.
Insomnia is associated with a reduction of natural killer (NK) activity in depression independent of the severity of other depressive symptoms. This study extends these findings by exploring the relationship between objective electroencephalographic (EEG) assessment of sleep and values of NK activity in depressed patients (n = 23) and in control subjects (n = 17). The sleep EEG parameters total sleep time, sleep efficiency, and duration of nonREM sleep were each positively correlated with NK activity in the depressed patients and in the control subjects, demonstrating similar relationships between the amount of sleep and NK activity in the separate groups. These observations support the hypothesis that sleep measures are associated with NK cytotoxicity, independent of the effects of severity of depressive symptoms or the presence of a mood disorder.
Stress reactions exist in many conditions in which plasma interleukin 6 (IL-6) is elevated. Examples are burns and sepsis. In these situations fever is often present. These stress situations are always accompanied with high levels of adrenalin and corticosteroids. These hormones, especially when given together, elicit a definite response of acute phase proteins in normal rats. In two stress models, (i) laparotomy and (ii) fever induced by administration of PGE2 in the lateral intracerebral ventricle, we observed a rise of adrenalin and corticosteron followed by an elevated level of plasma IL-6. Therefore, we studied the effect of adrenalin and corticosteron on the plasma level of IL-6. Adrenalin evokes high levels of IL-6, and this effect can be blocked by propranolol. When IL-6 release is blocked in this way, the response of alpha 2 macroglobulin and the cysteine protease inhibitor, both fast-reacting acute phase proteins in rat, is strongly depressed. Isoprenalin, an adreno beta 2 agonist, also causes very high levels of IL-6, indicating that the release of IL-6 can be mediated by an adreno beta 2 receptor whose presence has been demonstrated in monocytic cells. The results suggest a relation between stress situations and IL-6 and may be another factor besides the presence of endotoxins, virus, etc. explaining the high levels of IL-6 observed in many serious clinical situations.
Different helper T cell subsets secrete different patterns of cytokines when stimulated by antigen. The TH1 and TH2 subsets differ in the secretion of at least eight cytokines, and three or more other cytokine secretion patterns also exist among both mouse and human T cell clones. Several properties of strong immune responses suggest that at least the TH1 and TH2 phenotypes can be present in vivo. As cytokines are major determinants of the functions of the T cells that produce them, these patterns lead to different properties of the T cell subsets. TH1 cells mediate several functions connected with cytotoxicity and local inflammatory reactions, and so these T cells are particularly effective at combating viruses and intracellular bacteria and parasites. TH2 cells are much more effective at stimulating B cells to produce antibody, and so should be more effective against free-living bacteria, and in inducing protective humoral immunity. Antibody and delayed inflammatory reactions are often mutually exclusive during immune responses, and this can be at least partially explained by cross-inhibition of TH1 and TH2 cells. A newly discovered cytokine, IL10, has been implicated as one of the cross-regulatory cytokines, as this TH2 product inhibits cytokine synthesis by TH1 cells.
Rats received various doses of interleukin 1 (IL-1) (range, 0.5-25.0 ng) or pyrogen-free saline intracerebroventricularly during the rest (light) and the active (dark) cycles of the day, and sleep-wake activity and brain temperature were determined for 6 h. Low doses of IL-1 (0.5 ng at night, 2.5 ng during the day) increased both the duration of non-rapid-eye-movement sleep (NREMS) and electroencephalogram (EEG) slow-wave activity during NREMS episodes. Increasing doses of IL-1 had divergent effects on NREMS duration and EEG slow-wave activity, and the direction of the changes depended on the diurnal cycle. Thus NREMS duration was promoted at night and EEG slow-wave amplitudes during the day, whereas NREMS duration during the day and EEG slow-wave amplitudes at night were suppressed after higher doses of IL-1. High doses of IL-1 also induced decreases in rapid-eye-movement sleep during both phases of the day. Each dose of IL-1 that promoted NREMS also tended to increase brain temperature. These results demonstrate that IL-1 promotes NREMS in the rat. However, unlike previously reported findings in rabbits, the circadian rhythm of sleep regulation strongly interferes with the sleep-promoting activity of IL-1 in rats.
Sleep onset growth hormone secretion is a reliable and reproducible finding in young adults and children. Secretion typically occurs during the first non-REM period of sleep and, despite some evidence to the contrary, growth hormone secretion has frequently been associated with the first period of slow wave sleep. By measuring delta wave activity (0.5-2 Hz) instead of slow wave sleep and, accounting for the within subject variability, it has not been possible to demonstrate a consistent or statistically significant linear relationship between delta wave activity and sleep-related growth hormone secretion. This suggests the presence of more complex mediating factors and the possibility that sleep onset and growth hormone secretion are two separate processes which are independently stimulated by events associated with sleep onset.
Studies of cytotoxicity by human lymphocytes revealed not only that both allogeneic and syngeneic tumor cells were lysed in a non-MHC-restricted fashion, but also that lymphocytes from normal donors were often cytotoxic. Lymphocytes from any healthy donor, as well as peripheral blood and spleen lymphocytes from several experimental animals, in the absence of known or deliberate sensitization, were found to be spontaneously cytotoxic in vitro for some normal fresh cells, most cultured cell lines, immature hematopoietic cells, and tumor cells. This type of nonadaptive, non-MHC-restricted cellmediated cytotoxicity was defined as “natural” cytotoxicity, and the effector cells mediating natural cytotoxicity were functionally defined as natural killer (NK) cells. The existence of NK cells has prompted a reinterpretation of both the studies of specific cytotoxicity against spontaneous human tumors and the theory of immune surveillance, at least in its most restrictive interpretation. Unlike cytotoxic T cells, NK cells cannot be demonstrated to have clonally distributed specificity, restriction for MHC products at the target cell surface, or immunological memory. NK cells cannot yet be formally assigned to a single lineage based on the definitive identification of a stem cell, a distinct anatomical location of maturation, or unique genotypic rearrangements.
Serial sampling of peripheral blood from six healthy adult male volunteers was performed during daytime waking and nighttime sleeping. In addition, sleep physiology was assessed in all subjects (Ss) and sleep stages scored blind by standard criteria. Samples of plasma were analyzed for cortisol (Co) levels, functional interleukin-1 (IL-1), and interleukin-2 (IL-2) activity. Peripheral blood monocytes (PBM) were assayed to evaluate natural killer (NK) activity and mitogen responsiveness. Dramatic increase in IL-1 activity along with changes in other immune functions occurred during sleep and were related to onset of slow wave sleep.
Interleukin-10 (IL-10), originally designated a cytokine synthesis inhibitory factor, inhibits the synthesis of the pro-inflammatory cytokines IL-1 and tumor necrosis factor by stimulated human and mouse monocytes/macrophages; these cytokines are involved in the regulation of sleep. To determine if IL-10 reduces spontaneous sleep, we injected murine recombinant IL-10 intracerebroventricularly into rats prior to light onset. Non-rapid eye movements sleep was reduced. The behavioral responses to IL-10 were abolished by heat-inactivation of this cytokine. We believe these to be the first observations of central nervous system actions for this cytokine. These results further support the hypothesis that cytokines are involved in the regulation of sleep, and suggest an additional mechanism whereby sleep may be altered in response to an activated immune system.
Sleep disturbance, measured by either subjective report or electroencephalographic (EEG) assessment of sleep, correlates with a reduction of natural killer (NK) cell activity in major depression. To test whether sleep loss independent of mood disturbance alters daytime values of cellular immune function, the effect of late-night partial sleep deprivation on NK cell activity was studied in 23 medically and psychiatrically healthy male volunteers. After a night of sleep deprivation between 3 and 7 AM, NK cell activity was reduced in 18 of the 23 subjects with average lytic activity reduced significantly (p < .01) to a level 72% of the mean of three separate baseline values. After a night of resumed nocturnal sleep, NK cell activity had returned to baseline levels. These data implicate sleep in the modulation of natural immunity and demonstrate that even modest disturbances of sleep produce a reduction of NK cell activity.
Interleukin-1 (IL-1) is somnogenic and is hypothesized to be involved in physiological sleep regulation. Antibodies directed against rat IL-1 beta were used to further elucidate possible contributions of IL-1 to sleep regulation. Rabbit anti-rat IL-1 beta (anti-IL-1 beta) was injected intracerebroventricularly into normal rats 15 min before light onset. A 20-microgram dose of anti-IL-1 beta reduced non-rapid-eye-movement (NREM) sleep by 60 min during the subsequent 12-h slight period. There was no effect on rapid eye movement sleep after this dose of anti-IL-1 beta. The effects of anti-IL-1 beta on the enhancement of sleep after periods of sleep deprivation were also determined. When rats were deprived of sleep for 3-h beginning at light onset, the amount of time spent in NREM sleep increased for the remaining 9 h of the light period, regardless of whether control intracerebroventricular injections of pyrogen-free saline or rabbit immunoglobulin G were given during the deprivation period. However, when 20 micrograms anti-IL-1 beta were injected intracerebroventricularly during the sleep deprivation period, the expected NREM sleep rebound was completely blocked. Collectively, these data provide additional support for the hypothesis that IL-1 is involved in regulation of physiological sleep-wake activity.
Adrenaline, which is secreted from the adrenal medulla during stress, is considered to be involved in the control of inflammation and immune responses. Therefore, we studied the effects of adrenaline on the plasma levels of one of the major pro-inflammatory cytokines, interleukin-6 (IL-6). Here we describe that in rats, SC administration of adrenaline induces a dose-dependent increase in plasma IL-6 concentrations, reaching its maximum after 2 h. In addition, intravenous (IV) infusion of adrenaline in a dose resulting in circulating adrenaline concentrations similar to those observed during stress, enhanced heart rate and increased plasma IL-6 concentrations. The increase in plasma IL-6 in response to adrenaline given by subcutaneous (SC) route and by IV infusion could be blocked by the beta-adrenergic receptor antagonist l-propranolol but not by d-propranolol. Based on these data we conclude that under physiological conditions circulating adrenaline may be involved in the control of IL-6 production, and thereby may modulate inflammatory responses.
Of 288 patients with alcoholism and various stages of alcoholic hepatitis, 18.4% (53 of 288) reacted serologically for hepatitis C (HCV). An evaluation of the risk factors associated with HCV indicated that parenteral drug use, even in the distant past, increased the risk for infection 10.1-fold (p = 0.0001). Ethnicity was also a significant, independent risk factor. Minorities (i.e., African-Americans or Hispanic-Americans) had a 2.4-fold increase (p = 0.038). Prior blood transfusions, even if multiple, showed only a tendency toward increased infections (p = 0.088) in this population. An interaction between age and contact with parenteral drug users was demonstrated such that the risk of HCV infection was increased by contact with drug users. This was further increased with increasing age (p = 0.006). There was no relationship between HCV reactivity and the severity of the liver disease; however, the