alpha-Tocopherol supplementation decreases production of superoxide and cytokines by leukocytes ex vivo in both normolipidemic and hypertriglyceridemic individuals

Background: alpha-Tocopherol plays an important role in protecting LDL agai nst oxidation. However, additional effects of alpha-tocopherol at the intra cellular level may contribute to the clinical outcome of intervention studi es. Objective: We investigated whether alpha-tocopherol influences the inflamma tory responses of immune cells in normolipidemic and hypertriglyceridemic s ubjects. Design: RRR-alpha-Tocopherol was administered for 6 wk at a dose of 600 IU (402 mg)/d to 12 primary hypertriglyceridemic and 8 normolipidemic (fasting triacylglycerol >3.0 and <2.0 mmol/L, respectively) subjects. Cytokine pro duction [tumor necrosis factor or (TNF-alpha), interleukin (IL)-1 beta, and IL-8] by mononuclear cells and superoxide production by polymorphonuclear cells and in diluted whole blood were determined before and after the inter vention. Results: Cytokine and superoxide production did not differ significantly be tween hypertriglyceridemic and normolipidemic subjects. alpha-Tocopherol su pplementation resulted in a 2- to 3-fold increase in the concentration of a lpha-tocopherol in plasma and LDL. Whereas superoxide production in respons e to phorbol 12-myristate 13-acetate decreased in all subjects, response to oxidized LDL increased in 19 of 20 subjects. Response to opsonized zymosan before alpha-tocopherol supplementation was not significantly different fr om that after supplementation. Lipopolysaccharide-induced cytokine producti on by mononuclear cells decreased after supplementation with alpha-tocopher ol. Conclusions: alpha-Tocopherol differentially influences inflammatory respon ses of immune cells. These effects of alpha-tocopherol may be relevant in c hronic inflammatory processes such as atherogenesis.