Effects of RRR-α-Tocopheryl Succinate on IL-1 and PGE2 Production by Avian Macrophages
Vitamin E is an immunoregulatory agent that enhances both cellular and humoral immunity. Vitamin E has been postulated to function as a potent immune enhancer by increasing stimulatory cytokine production and by down-regulating suppressive prostaglandin synthesis. In an effort to better understand the mechanism whereby vitamin E ameliorates retrovirus-induced immune suppression, studies of vitamin E’s effects on macrophages and their soluble products were conducted. PGE2 levels produced by avian peritoneal exudate cells (PEC) cultured with avian erythroblastosis virus (AEV) in the presence or absence of vitamin E succinate were quantitated by a radioimmunometric assay. Interleukin-1 (IL-1) levels were quantified by a thymocyte co-mitogenesis assay using the avian macrophage cell line, HD11, cultured with and without vitamin E succinate supplementation. Supernatant from PEC obtained from normal chickens, exposed to AEV for 45 minutes, exhibited a 256% increase in the levels of PGE2 when compared to replica PEC cultures not exposed to AEV. Pretreatment of PEC with different amounts of vitamin E succinate prior to exposure to AEV decreased PGE2 levels in a dose dependent manner. PEC cultured with AEV and with 0.1 and 0.01 μg/ml of vitamin E succinate exhibited 55% and 77% reductions in PGE2 levels, respectively. Vitamin E succinate treated HD11 cells exhibited IL-1 activity 196% greater than that observed with untreated and vehicle controls. Vitamin E succinate and lipopolysaccharide (LPS) acted synergistically to increase IL-1 activity. LPS treatment alone gave a stimulation index 135% higher than controls, while a combination of LPS and vitamin E succinate gave a stimulation index 220% higher than controls. Down regulation of negative immune function regulator, PGE2, and upregulation of positive immune function regulator, IL-1, by vitamin E succinate could account for the ability of vitamin E succinate to ameliorate AEV-induced immune suppression.