Abstract
Zinc is an essential trace element with a critical role in normal growth and development and in immune homeostasis. Zinc deficiency impairs both the innate and the adaptive immune system and can be normalized by zinc supplementation. On the other end of the spectrum, high dosages of zinc diminish immune cell functions similar to zinc deficiency. Here, we investigated the influence of zinc aspartate on proliferation and cytokine production of stimulated human T cells and mouse splenocytes in vitro. Furthermore, the effect of zinc aspartate was examined in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of Multiple Sclerosis (MS) with a Th1/Th17 T cell-mediated immunopathogenesis. Zinc aspartate suppressed proliferation as well as IL-2, IL-10 and IL-17 production in stimulated human T cells and mouse splenocytes. Importantly, administration of a medium range dose of 30 μg/day zinc aspartate [1.5 mg/kg body weight (BW)] in a therapeutic manner led to a significant reduction of the clinical severity of the EAE during the first relapse of the disease. A lower zinc aspartate dose (6 μg/day, 0.3 mg/kg BW) had no significant therapeutic effect on the severity of the EAE, while administration of higher zinc aspartate amounts (120 μg/day, 6 mg/kg BW) led to more severe disease. Taken together, our data suggest that zinc aspartate can modulate activation, proliferation and cytokine production of effector T cells in vitro and in vivo and that activated autoreactive T cells may be potential therapeutic targets of tightly controlled zinc supplementation in autoimmune diseases like MS.
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Abbreviations
- BW:
-
Body weight
- CFA:
-
Complete Freund’s adjuvant
- CNS:
-
Central nervous system
- EAE:
-
Experimental autoimmune encephalomyelitis
- ELISA:
-
Enzyme-linked immunosorbent assay
- IL:
-
Interleukin
- i.p:
-
Intraperitoneal
- MLC:
-
Mixed lymphocyte cultures
- MS:
-
Multiple sclerosis
- NK:
-
Natural killer
- PBMC:
-
Peripheral blood mononuclear cells
- PLP:
-
Proteolipid protein
- PWM:
-
Pokeweed mitogen
- PTX:
-
Pertussis toxin
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Stoye, D., Schubert, C., Goihl, A. et al. Zinc aspartate suppresses T cell activation in vitro and relapsing experimental autoimmune encephalomyelitis in SJL/J mice. Biometals 25, 529–539 (2012). https://doi.org/10.1007/s10534-012-9532-z
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DOI: https://doi.org/10.1007/s10534-012-9532-z