Modulating the immune response by oral zinc supplementation: A single approach for multiple diseases

Institute of Immunology, RWTH Aachen University Hospital, Aachen, Germany.
Archivum Immunologiae et Therapiae Experimentalis (Impact Factor: 3.18). 02/2008; 56(1):15-30. DOI: 10.1007/s00005-008-0003-8
Source: PubMed


Zinc is required for multiple cellular tasks, and especially the immune system depends on a sufficient availability of this essential trace element. During the last decades, many studies attempted to affect the outcome of various diseases by zinc supplementation. These efforts either aimed at supporting immunity by zinc administration or at correcting a loss of zinc secondary to the disease to restore the zinc-dependent functions of the immune system. This review aims to summarize the respective findings and to discuss possible molecular mechanisms by which zinc could influence viral, bacterial, and parasitic infections, autoimmune diseases, and the response to vaccination. Zinc supplementation in diseases such as diarrhea, chronic hepatitis C, shigellosis, leprosy, tuberculosis, pneumonia, acute lower respiratory infection, and leishmaniasis seems beneficial. In contrast, the results for the common cold and malaria are still not conclusive, and zinc was ineffective in most vaccination and rheumatoid arthritis studies. For AIDS and type 1 diabetes, zinc supplementation may even be a risk factor for increased mortality or deterioration of the glucose metabolism, respectively. In these cases, zinc supplementation should be used with care and limited to clearly zinc-deficient individuals.

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    • "For example, Zn mediates antiviral effects through the inhibition of nidovirus RNA-dependent RNA polymerases or other proteins essential for the different phases of the viral life cycle [5,6]. In addition, Zn participates in initiating and maintaining robust immune responses, in particular cytokine production and modulation of the activity of immune cells [7]. Zn induces the production of innate interferon (IFN)-α and also immune IFN-γ, and can potentiate the antiviral action of IFN-α, but not of IFN-γ [8]. "
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    ABSTRACT: Zinc (Zn) supplementation has been shown to reduce the incidence of diarrhea and to protect animals from intestinal diseases, but the mechanisms of this protective effect against virus infection in vivo have not yet been elucidated. Transmissible gastroenteritis virus (TGEV) causes diarrhea in piglets with an age-dependent decrease of severity. We used 60 weaned piglets that were divided into three groups to evaluate the effect of different Zn levels added to a conventional diet (50 mg Zn/kg diet, Znlow, control group). The other groups received the diet supplemented with ZnO at final concentrations of 150 mg Zn/kg diet (Znmed), or 2,500 mg/kg diet (Znhigh). Oral challenge infection with TGEV was performed when the pigs had been fed for 1 week with the respective diet. Half of the piglets of each group were sacrificed at day 1 and 18 after challenge infection. Fecal consistency was improved and body weights increased in the Znhigh group when compared to the other groups, but no direct effect of Zn concentrations in the diet on fecal TGEV shedding and mucosal immune responses was detectable. However, in the Znhigh group, we found a prevention of villus atrophy and decreased caspase-3-mediated apoptosis of jejunal epithelium. Furthermore, pigs receiving high Zn diet showed a down-regulation of interferon (IFN)-alpha, oligoadenylate synthetase (OAS), Zn transporter SLC39A4 (ZIP4), but up-regulation of metallothionein-1 (MT1), as well as the Zn transporters SLC30A1 (ZnT1) and SLC30A5 (ZnT5). In addition, forskolin-induced chloride secretion and epithelial resistance were controlled at a physiological level in the Znhigh but not the other groups. Finally, in the Znhigh group, we documented an earlier and higher systemic TGEV-specific serum antibody response. These results suggest that high dietary Zn could provide enhanced protection in the intestinal tract and stimulate the systemic humoral immune response against TGEV infection.
    Full-text · Article · Mar 2014 · BMC Veterinary Research
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    • "Because of the considerable impact of zinc on specific and nonspecific immune responses, its deficiency can lead to reduction of appropriate responses.[3637383940414243] "
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    ABSTRACT: Immunotherapy with paternal lymphocytes plays an important role in preventing recurrent spontaneous abortion (RSA) and is an effective treatment for it. This kind of treatment is performed as an immunotherapy method in several centers in the world. It attributes to the production of anti-paternal cytotoxic antibodies (APCAs) in women with RSA. Production of APCA after lymphocyte immunotherapy (LIT) in RSA patients gives them a better chance for successful pregnancy. Regarding the important effect of trace elements on the function of the immune system, we tried to investigate the correlation between serum zinc level and the success of LIT in RSA. Serum zinc concentration was determined in two groups of RSA patients using atomic absorption spectrophotometer systems. Group (a) that responded to the paternal lymphocytes and their cross-match test was positive, and group (b) that had no response to the paternal lymphocytes immunizations and their cross-match test was negative. Serum zinc levels in group (a) patients were 74.98 ± 11.88 μg/dl, which was significantly higher than those in group (b) with the zinc concentration of 64.22 ± 9.22 μg/dl. Zinc deficiency may be one of the substantial causes of negative results for LIT in RSA patients. Therefore, compensation of zinc defect before LIT can be a promising approach to improve the immune response in patients.
    Full-text · Article · Mar 2013 · Journal of Human Reproductive Sciences
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    • "Zinc is also found in non-enzymatic contexts in humans, for example its structural role in the ubiquitous zinc finger transcriptional regulators [7]. Zinc is also important for immune function, and zinc deficiency adversely affects the health and development of children [8,9]. However, a double-blind, randomized, controlled study involving 937 children with acute diarrhoea conducted in New Delhi, India demonstrated that zinc supplementation benefited children in the experimental group irrespective of the child’s initial plasma zinc level [5]. "
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    ABSTRACT: Dietary supplementation with zinc has been shown to reduce the duration and severity of diarrhoeal disease caused by Enteropathogenic Escherichia coli, common in infants in developing countries. Initially this therapeutic benefit was attributed to the correction of zinc deficiency in malnourished individuals, but recently evidence has emerged that zinc significantly impacts the pathogens themselves: zinc concentrations achievable by oral supplementation can reduce the expression of key virulence-related genes in EPEC and related organisms. Here, we investigate three possible mechanisms for such zinc-induced changes in expression of EPEC virulence: direct interaction of zinc with regulators of LEE operons; genetic interaction of LEE operons with known regulators of zinc homeostasis; and finally, downregulation of LEE transcription associated with activation of the σEenvelope stress response by zinc. We find evidence only for the latter mechanism, including zinc-induced down-regulation of type III secretion in EPEC similar to that caused by ammonium metavanadate, another known inducer of the σEstress response. We conclude therefore that envelope stress is a major mechanism by which zinc attenuates the virulence of EPEC and related pathogens.
    Full-text · Article · Jun 2012 · BMC Microbiology
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