Interleukin-4 Administration or Zinc Supplementation Is Effective in Preventing Zinc Deficiency-Induced Hemolytic Anemia and Splenomegaly.

Nutritional zinc deficiency aggravates inflammation, subsequently causing anemia and splenomegaly in rats; however, the mechanism underlying such splenomegaly remains poorly understood. Therefore, in this study, we aimed to elucidate the mechanisms underlying the splenomegaly and anemia occurring in zinc-deficient rats and investigate whether these effects of zinc deficiency could be reversed by interleukin (IL)-4 administration or zinc supplementation. Five-week-old male Sprague-Dawley rats were fed a standard diet; fed a zinc-deficient diet (n = 7 each) and injected with saline or IL-4; or fed a zinc-deficient diet for 6 weeks followed by a standard diet for 4 weeks thereafter. White blood cells, segmented neutrophils, platelets, CD4 T cells, CD11b/c granulocytes, CINC/GRO cells, and myeloperoxidase-positive cells in the blood and spleen of the zinc-deficient rats were significantly higher than those in all the other groups. Conversely, red blood cells, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, lymphocytes, and CD8 T cells in the blood of the zinc-deficient rats were significantly lower than those in the other groups. Furthermore, serum aspartate aminotransferase, lactate dehydrogenase, indirect bilirubin concentrations, and erythrocyte osmotic fragility in the zinc-deficient rats were significantly higher than those in the other groups. Moreover, zinc deficiency significantly decreased the GATA1 protein levels in the spleen. Collectively, these results indicate that zinc deficiency aggravates the inflammatory response and causes hemolytic anemia and splenomegaly. Importantly, IL-4 administration and zinc supplementation can reverse the zinc deficiency-induced hemolytic anemia and splenomegaly.