Inflammatory response under zinc deficiency is exacerbated by dysfunction of the Th2 lymphocyte - M2 macrophage pathway.

Nutritional zinc deficiency leads to immune dysfunction and aggravates inflammation. However, the underlying mechanism remains unknown. In this study, the relationship between macrophage subtypes (M1 and M2) or helper T lymphocytes (Th1 and Th2) were investigated using the spleen from rats fed zinc-deficient or standard diet. In experiment I, five-week-old male Sprague-Dawley rats were fed zinc-deficient diet (without zinc additives) or standard diet (containing 0.01% zinc) for 6 weeks. In experiment II, the rats were divided into four groups: one group was fed a standard diet for 6 weeks; two groups were fed zinc-deficient diet and were injected three times a week with either saline or interleukin (IL)-4 (zinc-deficient/IL-4 i.p.); a fourth group (zinc-deficient/standard) was fed a zinc-deficient diet for 6 weeks followed by a standard diet for 4 weeks. In experiment I; GATA-3 protein level, M2 macrophage, CD3+ CD8+ cell, and IL-4/IL-13-positive cells significantly decreased in the spleens of zinc-deficient group. Additionally, IL-1β and MIP-1α mRNA levels significantly increased in the splenic macrophages of zinc-deficient group. In experiment II; M2 macrophages, CD3+ CD8+ cells, IL-4/IL-13-positive cells, and GATA-3 protein levels signfiicantly increased in the spleens of the zinc-deficient/IL-4 i.p. and zinc-deficient/standard groups. Furthermore, IL-1β and MIP-1α mRNA levels decreased in the splenic macrophages of the zinc-deficient/IL-4 i.p. and zinc-deficient/standard groups. Zinc deficiency-induced aggravated inflammation is related to Th2 lymphocytes and followed by the association with loss of GATA-3, IL-4, and anti-inflammatory M2 macrophages. Importantly, IL-4 injection or zinc supplementation can reverse the effects of zinc deficiency on immune function. This article is protected by copyright. All rights reserved.