No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Zinc and copper in serum and induced sputum of patients with allergic rhinitis and allergic asthma
Abstract
Background: Zinc was shown to have protective effect on the respiratory system, so it may play a role in allergic airway diseases. The aim of our study was to measure zinc and copper levels in serum and induced sputum in patients with allergic rhinitis and patients with allergic asthma. Methods: We measured concentrations of zinc and copper in serum and in supernatant of induced sputum in 21 patients with allergic asthma, in 13 patients with allergic rhinitis and in 10 control subjects. Results: We have found decreased levels of zinc in serum of patients with allergic asthma and in patients with allergic rhinitis. Furthermore, levels of zinc in serum in patients with allergic asthma were lower than in patients with allergic rhinitis. Concentrations of zinc in supernatant of induced sputum were lower in asthmatics than in control subjects and rhinitics, but this difference was not statistically significant. There was no significant difference in concentrations of copper in serum and in sputum between asthmatics, rhinitics and control subjects. We have also found a positive linear correlation between zinc concentrations in serum and sputum in the group of control subjects, in patients with allergic asthma and in male patients with allergic rhinitis. Conclusion: We conclude that zinc deficiency was confirmed both in patients with allergic asthma and in patients with allergic rhinitis.
ResearchGate has not been able to resolve any citations for this publication.
Background
Antioxidant supplementation is thought to improve immunity and thereby reduce infectious morbidity. However, few large trials in elderly people have been conducted that include end points for clinical variables.Objective
To determine the effects of long-term daily supplementation with trace elements (zinc sulfate and selenium sulfide) or vitamins (beta carotene, ascorbic acid, and vitamin E) on immunity and the incidence of infections in institutionalized elderly people.Methods
This randomized, double-blind, placebo-controlled intervention study included 725 institutionalized elderly patients (>65 years) from 25 geriatric centers in France. Patients received an oral daily supplement of nutritional doses of trace elements (zinc and selenium sulfide) or vitamins (beta carotene, ascorbic acid, and vitamin E) or a placebo within a 2×2 factorial design for 2 years.Main Outcome Measures
Delayed-type hypersensitivity skin response, humoral response to influenza vaccine, and infectious morbidity and mortality.Results
Correction of specific nutrient deficiencies was observed after 6 months of supplementation and was maintained for the first year, during which there was no effect of any treatment on delayed-type hypersensitivity skin response. Antibody titers after influenza vaccine were higher in groups that received trace elements alone or associated with vitamins, whereas the vitamin group had significantly lower antibody titers (P<.05). The number of patients without respiratory tract infections during the study was higher in groups that received trace elements (P=.06). Supplementation with neither trace elements nor vitamins significantly reduced the incidence of urogenital infections. Survival analysis for the 2 years did not show any differences between the 4 groups.Conclusions
Low-dose supplementation of zinc and selenium provides significant improvement in elderly patients by increasing the humoral response after vaccination and could have considerable public health importance by reducing morbidity from respiratory tract infections.
The term “allergen tachyphylaxis” (AT) describes a progressively decreased bronchial reactivity to allergen exposition after repeated allergen challenge [in our test system measured by sequential inhalative antigen challenge of sensitized guinea pigs (GP)]. The hypothesis that AT is mediated by endogenous prostaglandin E (PGE) biosynthesis was tested in vivo on GP sensitized to ovalbumin (OA).
Different groups of animals were challenged with simultaneous inhalation of OA (repeatedly at time 0, 10, 20, 60 and 70 min) together with inhibitors of PGE-biosynthesis (parachloromercurobenzoic acid = PCMB, copper sulfate = Cu, copper dithiotreitol complex = CuDTT, dithiotreitol = DTT and dimercaptopropanol = DMP) or agents increasing PGE production (aurothioglucose = Au, zinc dithiotreitol complex = ZnDTT and reduced glutathion = GSH). Bronchial obstruction was measured by whole body plethysmography. PCMB, Cu, CuDTT, DTT and DMP inhibited AT, whereas Au and ZnDTT enhanced AT. Acetylsalicylic acid (ASA) treatment prevented AT. Aerosols of PGE2, but not of prostacyclin or prostaglandin D2 restored AT in ASA treated animals.
In addition to these in vivo experiments in vitro investigations showed that PCMB, Cu and DTT decreased while ZnDTT increased PGE biosynthesis of allergen challenged GP lungs. It is concluded that AT, an important self-protecting mechanism of GP bronchial asthma, is mediated at least in part via endogenous PGE.
The immune system acts to protect the host from infectious agents that exist in the environment (bacteria, viruses, fungi, parasites) and from other noxious insults. The immune system is constantly active, acting to discriminate 'non-self' from 'self'. The immune system has two functional divisions: the innate and the acquired. Both components involve various blood-borne factors (complement, antibodies, cytokines) and cells. A number of methodologies exist to assess aspects of immune function; many of these rely upon studying cells in culture ex vivo. There are large inter-individual variations in many immune functions even among the healthy. Genetics, age, gender, smoking habits, habitual levels of exercise, alcohol consumption, diet, stage in the female menstrual cycle, stress, history of infections and vaccinations, and early life experiences are likely to be important contributors to the observed variation. While it is clear that individuals with immune responses significantly below 'normal' are more susceptible to infectious agents and exhibit increased infectious morbidity and mortality, it is not clear how the variation in immune function among healthy individuals relates to variation in susceptibility to infection. Nutrient status is an important factor contributing to immune competence: undernutrition impairs the immune system, suppressing immune functions that are fundamental to host protection. Undernutrition leading to impairment of immune function can be due to insufficient intake of energy and macronutrients and/or due to deficiencies in specific micronutrients. Often these occur in combination. Nutrients that have been demonstrated (in either animal or human studies) to be required for the immune system to function efficiently include essential amino acids, the essential fatty acid linoleic acid, vitamin A, folic acid, vitamin B6, vitamin B12, vitamin C, vitamin E, Zn, Cu, Fe and Se. Practically all forms of immunity may be affected by deficiencies in one or more of these nutrients. Animal and human studies have demonstrated that adding the deficient nutrient back to the diet can restore immune function and resistance to infection. Among the nutrients studied most in this regard are vitamin E and Zn. Increasing intakes of some nutrients above habitual and recommended levels can enhance some aspects of immune function. However, excess amounts of some nutrients also impair immune function. There is increasing evidence that probiotic bacteria improve host immune function. The effect of enhancing immune function on host resistance to infection in healthy individuals is not clear.
Asthma is characterized by an increased production of eosinophil-active C-C chemokines by the airway epithelium. Recent studies have identified the presence of important quantities of labile zinc in the conducting airways. We hypothesized that modulation of this labile zinc could influence the production of proinflammatory chemokines in respiratory epithelial cells. The zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and the heavy metal chelator 2,3-dimercapto-1-propanesulfonic acid (DMPS) were used to reduce the labile zinc content of A549, BEAS-2B, and HFL-1 cells. Northern blot analysis and RNase protection assay were used to study the effects of the zinc chelators on mRNA expression. DMPS and TPEN specifically inhibited the production of eotaxin, regulated on activation, normal T-cell expressed, and presumably secreted, and monocyte chemotactic protein-1 in TNF-alpha-stimulated respiratory epithelial cells and fibroblasts through labile zinc chelation. The inhibitory effects of DMPS and TPEN were associated with the decreased binding of the zinc-finger transcription factor GATA-1, whereas no change in NF-kappaB activation was observed. Together these results demonstrate that modulation of the labile pool of zinc can regulate gene expression and protein synthesis of C-C chemokines in lung epithelial cells and fibroblasts.
The aim of the present study is to evaluate the status of plasma essential trace element selenium (Se), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) concentrations and the effect of these elements on oxidative status in patients with childhood asthma. Plasma Se, Mn, Cu, and Zn concentrations were determined by atomic absorption spectrophotometry (AAS) and Fe concentrations, malondialdehyde (MDA), and total antioxidant capacity (TAC) were determined by the colorimetric method. The plasma MDA/TAC ratio was calculated as an index of oxidative status. Plasma albumin levels were measured to determine nutritional status. Plasma Fe concentrations, MDA levels and the MDA/TAC ratio were significantly higher (p<0.001, p<0.001, and p<0.01, respectively) and Se and Mn concentrations and TAC were lower (p<0.01, p<0.05, and p<0.01, respectively) in patients when compared to the healthy subjects. Plasma Zn, Cu, and albumin levels were not found to be significantly different in patients and controls (p>0.05). There were positive relationships between plasma MDA and Fe (r=0.545, p<0.001) and TAC and Se (r= 0.485, p<0.021), and a negative correlation between TAC and MDA values (r= -0.337, p<0.031) in patients with childhood asthma. However, there was no correlation between these trace elements and albumin content in patient groups. These observations suggest that increased Fe and decreased Se concentrations in patients with childhood asthma may be responsible for the oxidant/antioxidant imbalance.
Thanks to progress in zinc research, it is now possible to describe in more detail how zinc ions (Zn++) and nitrogen monoxide (NO), together with glutathione (GSH) and its oxidized form, GSSG, help to regulate immune responses to antigens. NO appears to be able to liberate Zn++ from metallothionein (MT), an intracellular storage molecule for metal ions such as zinc (Zn++) and copper (Cu++). Both Zn++ and Cu++ show a concentration-dependent inactivation of a protease essential for the proliferation of the AIDS virus HIV-1, while zinc can help prevent diabetes complications through its intracellular activation of the enzyme sorbitol dehydrogenase (SDH). A Zn++ deficiency can lead to a premature transition from efficient Th1-dependent cellular antiviral immune functions to Th2-dependent humoral immune functions. Deficiencies of Zn++, NO and/or GSH shift the Th1/Th2 balance towards Th2, as do deficiencies of any of the essential nutrients (ENs)- a group that includes methionine, cysteine, arginine, vitamins A, B, C and E, zinc and selenium (Se) - because these are necessary for the synthesis and maintenance of sufficient amounts of GSH, MT and NO.
The study comprised 40 children of both sexes aged from 2 to 12 years, 22 suffering from bronchial asthma and 18 suffering from atopic dermatitis. Twenty healthy children of comparable age and sex to the patients were studied as controls. All the children were subjected to full history including dietetic questionnaire, thorough examination, and to estimation of serum IgE, serum ceruloplasmin, and zinc and copper levels in both serum and hairs. The mean concentrations of zinc in serum and hairs were respectively 70.3 +/- 13.2 micrograms/100 ml and 167.5 +/- 23.0 micrograms/gm in asthmatic cases and 65.9 +/- 11.7 micrograms/100 ml and 164.8 +/- 23.6 micrograms/gm in those with atopic dermatitis. These levels were significantly (p less than 0.001) decreased in comparison to the control values (88.4 +/- 11.0 micrograms/100 ml and 194.5 +/- 18.6 micrograms/gm). On the other hand, a significant (p less than 0.001) increase in serum and hairs copper was demonstrated in both allergic groups compared to the controls. Mean copper values were respectively 79.5 +/- 8.06 micrograms/100 ml and 18.7 +/- 1.9 micrograms/gm in the asthmatic cases and 81.4 +/- 8.4 micrograms/100 ml and 17.8 +/- 2.08 micrograms/gm in cases with atopic dermatitis. The control mean concentrations were 67.95 +/- 6.37 micrograms/100 ml and 14.5 +/- 2.53 micrograms/gm respectively. Significant (p less than 0.001) higher levels of serum ceruloplasmin were observed in the allergic patients compared to the controls and were correlated with the hypercupremia. The results were discussed and a good dietetic intake of high biological value protein and zinc supplement was recommended to these patients in order to correct their disturbances especially the hypozincemia which could lead to exaggeration of their allergic conditions. The field of trace elements metabolism has grown rapidly over the past few years, particularly after the development of novel techniques as the atomic absorption spectrophotometry which had allowed the reliable measurements of several trace elements in tissues and so had opened a new field for many researches (Henkin, 1976). Zinc and copper are involved in cell and tissue growth. Zinc plays an important role in DNA and protein synthesis and is intimately involved with copper as cofactors in several important enzyme systems. The effects of many pathological conditions as congestive heart failure, pneumonia, rheumatic heart diseases, bronchitis, recurrent infection, hemolytic anemia, psoriasis, and malnutrition on the levels of serum zinc, copper, and other trace elements have been of interest to investigators for a number of years (Sinha and Gabrieli, 1970; David et al., 1984).(ABSTRACT TRUNCATED AT 400 WORDS)
Zinc and copper status was examined in 19 healthy and 43 atopic children (22 asthmatics and 21 eczematous) 2-14 years old. Dietary intakes for energy, protein, zinc and copper and some nutritional indices (height, weight, serum protein, albumin, ceruloplasmin) were similar in the allergic and in the control group. The proton-induced X-ray fluorescence technique was used to assess zinc and copper concentrations in serum and hair. No difference was detected in serum zinc concentration between allergic and healthy children. In contrast, mean hair zinc level was lower (p less than 0.05) in allergic than in healthy children (99 +/- 6 vs. 147 +/- 9 micrograms/g). Mean serum copper content was higher in asthmatic than in control children while mean hair copper was higher (p less than 0.05) in asthmatic and eczematous children than in the control group. These findings suggest a different zinc and copper nutritional status between allergic and healthy subjects. Allergic children, in particular, seem to be a risk of zinc deficiency.
Free ionic zinc (Zn2+) in saliva shortens duration and severity of common cold (CC) symptoms. It is proposed that Zn2+ complexes with proteins of critical nerve endings and surface proteins of human rhinovirus (HRV) (a) interrupt nerve impulses and (b) block docking of HRV on intercellular adhesion molecule-1 (ICAM-1) on somatic cells, thereby interrupting HRV infection. Since leukocyte function associated antigen-1 (LFA-1) binds leukocytes to cells through ICAM-1, initiating inflammation, Zn2+ is expected to block LFA-1/ICAM-1 binding and thereby suppress inflammation. This could explain reduction of inflammation experienced by persons taking zinc gluconate/glycine (ZGG) lozenges for CC. Allergic rhinitis (AR) and CC share many common symptoms, and ZGG also mitigates AR symptoms. Focal irritation, increased ICAM-1 expression, and recruitment of leukocytes to epithelial foci are the common elements. Zinc ions may be an important anti-inflammatory factor because they can block docking of both HRV and LFA-1 with ICAM-1.
Results from well controlled animal and cellular experi- ments and limited clinical observations have demonstrated that the micronutrient copper is required for the normal development and function of cells in the innate and ac- quired arms of the immune system. However, the specific biochemical roles of copper in the maturation, activation, and effector activities of host defense cells remain un- known. In vitro studies with rodent splenocytes and the Jurkat human T cell line have shown that copper defi- ciency attenuates the ability of activated T cells to pro- duce sufficient quantities of interleukin-2 to promote nor- mal proliferation. Possible roles of copper in the expres- sion of the interleukin-2 gene are being investigated. Be- cause most investigators examining the link between cop- per and immunity have utilized severely copper-deficient models, the relevance of their findings for human health has been questioned. Recent studies demonstrating that the in vitro activities of T cells are compromised by mar- ginal copper deficiency in both adult rats and healthy human subjects suggest that suboptimal intake of this trace metal has the potential to attenuate resistance to infectious disease.
The objective of this study was to analyze the role of some trace metals in the immune system of nonallergic or atopic men. One of these elements (Zn) is essential for immune function, whereas others, present in the urban environment, are known to be allergenic (Ni and Cr) or toxic (Pb). Serum levels of interleukin (IL) 2, 4, 5, and 13 and of interferon-y and immunoglobulins, blood lymphocyte subsets, blood concentrations of Pb and Zn, serum levels of Zn, and urinary Cr and Ni concentrations were determined in 17 nonallergic men (mean age 34 years) and 17 healthy nonsymptomatic atopic men living in urban areas. The mean blood concentration of Pb (a marker of exposure to toxic agents) was 11 microg/dl in both groups, which showed similar levels of blood Zn and of urinary Ni and Cr, whereas the serum Zn concentration was lower in the atopic group. Serum IgE levels were much higher in atopic men than in nonallergics, whereas serum IL-2, IL-5, and IL-13 concentrations were lower, possibly due to binding to tissue receptors and cells. Moreover, in atopic subjects, numbers of blood CD4+-CD45RO-"virgin" lymphocytes were significantly lower and the CD4+ -CD45RO+/CD4+ -CD45RO- ratio was more elevated, indicating an activation of the immune system. Serum IgE levels of atopic men, in contrast to those of nonallergic subjects, were correlated with CD19+ and CD5--CD19+ B lymphocytes. Blood Pb levels of both groups of men were correlated with CD4+, CD4+-CD45RO+, and HLA-DR+ [activated T-, B-, CO4+ -C. and natural killer (NK) cells] lymphocytes; in particular, blood Pb levels of the nonallergic men were also significantly correlated with CD25+ cells activated by IL-2, whereas those of the atopic men were also correlated with CD3--HLA-DR+ (B- and NK-cells) and CD5--CD19+ lymphocytes. Besides serum Zn levels, urinary Ni and Cr of nonallergic men were correlated with several immune parameters; in particular, urinary Cr was correlated with serum IL-5 and IgE and urinary Ni was correlated with CD4+ -CD45RO+ and CD3+ -CD25+ lymphocytes. This correlation of Ni and Cr, also found in previous studies in nonallergic subjects, confirms the hypothesis that these metals are involved in mechanisms of immune response regulation and that allergy to Ni or Cr represents an alteration of physiological mechanisms. Previous experimental studies have demonstrated that Pb exerts immunomodulatory effects on CD4+ and B- lymphocytes, enhancing the production of Th2-like cytokines and IgE. These experimental results confirm those of this study, showing in atopic men the correlation of B-lymphocytes with both blood Pb and serum IgE levels. This suggests that Pb may enhance the incidence of atopy in populations exposed to an urban environment.
Because little is known about micronutrient/antioxidant intake and asthma severity, we investigated dietary intake and plasma/serum levels of micronutrients/antioxidants in a group of asthma patients with various degrees of severity, and compared the results with healthy subjects.
A case control study was carried out on 118 asthma patients and 121 healthy subjects. The severity of the disease was classified by division of patients into four groups. Normal dietary micronutrient/antioxidant intake was estimated from a food frequency questionnaire. Plasma/serum levels of vitamins C, E, and A, selenium, magnesium, zinc, and platelet glutathione peroxidase (GSH-Px) activity were also determined.
No differences in daily micronutrient/antioxidant intake were seen between patients and healthy subjects. The severity of the disease showed no significant relationship with micronutrient/antioxidant intake. There were no differences in plasma/serum levels in any of the micronutrients/antioxidants between healthy subjects and asthmatics. Nor were any differences found between asthma groups in severity in the biochemical measures, except in platelet GSH-Px activity, which was significantly lower in the most severe groups.
In this study, we found no evidence of any association between micronutrient/antioxidant intake or plasma/serum levels of micronutrients/antioxidants and asthma. Reduction of platelet GSH-Px activity in the most severe patients suggests that these patients have a diminished capacity to restore part of the antioxidant defences.
Over the past 30 years, many researchers have demonstrated the critical role of zinc (Zn), a group IIb metal, in diverse physiological processes, such as growth and development, maintenance and priming of the immune system, and tissue repair. This review will discuss aspects of Zn physiology and its possible beneficial role in the respiratory epithelium. Here we have detailed the mechanisms by which Zn diversely acts as: (i) an anti-oxidant; (ii) an organelle stabilizer; (iii) an anti-apopototic agent; (iv) an important cofactor for DNA synthesis; (v) a vital component for wound healing; and (vi) an anti-inflammatory agent. This paper will also review studies from the authors' laboratory concerning the first attempts to map Zn in the respiratory epithelium and to elucidate its role in regulating caspase-3 activated apoptosis. We propose that Zn, being a major dietary anti-oxidant has a protective role for the airway epithelium against oxyradicals and other noxious agents. Zn may therefore have important implications for asthma and other inflammatory diseases where the physical barrier is vulnerable and compromised.
Eosinophils play a primary role in the pathophysiology of asthma. In the lung, the activation state of the infiltrating eosinophils determines the extent of tissue damage. Interleukin-5 (IL-5) and leukotriene B4 (LTB4) are important signaling molecules involved in eosinophil recruitment and activation. However, the physiological processes that regulate these activation events are largely unknown. In this study we have examined the mechanisms of human eosinophil NADPH oxidase regulation by IL-5, LTB4, and phorbol ester (PMA). These stimuli activate a Zn2+-sensitive plasma membrane proton channel, and treatment of eosinophils with Zn2+ blocks superoxide production. We have demonstrated that eosinophil intracellular pH is not altered by IL-5 activation of NADPH oxidase. Additionally, PKCdelta inhibitors block PMA, IL-5 and LTB4 mediated superoxide formation. Interestingly, the PKCdelta-selective inhibitor, rottlerin, does not block proton channel activation by PMA indicating that the oxidase and the proton conductance are regulated at distinct phosphorylation sites. IL-5 and LTB4, but not PMA, stimulated superoxide production is also blocked by inhibitors of PI 3-kinase indicating that activation of this enzyme is an upstream event common to both receptor signaling pathways. Our results indicate that the G-protein-coupled LTB4 receptor and the IL-5 cytokine receptor converge on a common signaling pathway involving PI 3-kinase and PKCdelta to regulate NADPH oxidase activity in human eosinophils.
Zn may have an important protective role in the respiratory epithelium and Zn deficiency may enhance airway inflammation and epithelial damage. The effects of mild nutritional Zn deficiency on airway hyperresponsiveness (AHR) and airway inflammation in mice sensitized and challenged with ovalbumin (OVA) to induce an allergic response were investigated. Balb/c mice were given Zn normal (ZN, 50 mg/kg Zn) or Zn limited diets (ZL, 14 mg/kg Zn) before and during induction of allergic airway inflammation, with appropriate controls (saline-treated, SAL). ZL mice had greater levels of AHR than ZN mice, regardless of presence or absence of allergic inflammation. These mice also had increased eosinophilia and mucus cell hyperplasia compared with ZN mice. Second, ZN and ZL OVA-treated mice had significant decreases in airway epithelial Zinquin fluorescence, indicating a lowered availability of Zn compared with their SAL-treated counterparts. In contrast, the pro-apoptotic protein caspase-3, which was co-localized with Zn in the apical epithelium, was significantly increased in both ZN and ZL OVA-treated mice. Immunologically active caspase-3 and apoptosis were increased in OVA-treated mice, especially the ZL group. These findings provide the first data for adverse effects of Zn deficiency on the respiratory epithelium and support a role for altered Zn homeostasis and caspase upregulation in asthma.
There is ample evidence that allergic disorders, such as asthma, rhinitis, and atopic dermatitis, are mediated by oxidative stress. Excessive exposure to reactive oxygen and nitrogen species is the hallmark of oxidative stress and leads to damage of proteins, lipids, and DNA. Oxidative stress occurs not only as a result of inflammation but also from environmental exposure to air pollution and cigarette smoke. The specific localization of antioxidant enzymes in the lung and the rapid reaction of nitric oxide with reactive oxygen species, such as superoxide, suggest that antioxidant enzymes might also function as cell-signaling agents or regulators of cell signaling. Therapeutic interventions that decrease exposure to environmental reactive oxygen species or augment endogenous antioxidant defenses might be beneficial as adjunctive therapies for allergic respiratory disorders.
Antioxidants play a critical role in keeping skin healthy. The antioxidant benefits of vitamin C and E are well known, but the importance of the trace mineral, zinc, has been overlooked. This article reviews the evidence supporting zinc's antioxidant role in protecting against free radical-induced oxidative damage. Zinc protects against UV radiation, enhances wound healing, contributes to immune and neuropsychiatric functions, and decreases the relative risk of cancer and cardiovascular disease. All body tissues contain zinc; in skin, it is five to six times more concentrated in the epidermis than the dermis. Zinc is required for the normal growth, development and function of mammals. It is an essential element of more than 200 metalloenzymes, including the antioxidant enzyme, superoxide dismutase, and affects their conformity, stability, and activity. Zinc also is important for the proper functioning of the immune system, and for glandular, reproductive and cell health.
Abundant evidence demonstrates the antioxidant role of zinc. Topical zinc, in the form of divalent zinc ions, has been reported to provide antioxidant photoprotection for skin. Two antioxidant mechanisms have been proposed for zinc: zinc ions may replace redox active molecules, such as iron and copper, at critical sites in cell membranes and proteins; alternatively, zinc ions may induce the synthesis of metallothionein, sulfhydryl-rich proteins that protect against free radicals. No matter how they work, topical zinc ions may provide an important and helpful antioxidant defense for skin.