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BACKGROUND: alpha-Tocopherol plays an important role in protecting LDL against oxidation. However, additional effects of alpha-tocopherol at the intracellular level may contribute to the clinical outcome of intervention studies. OBJECTIVE: We investigated whether alpha-tocopherol influences the inflammatory responses of immune cells in normolipidemic and hypertriglyceridemic subjects. 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 production [tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-8] by mononuclear cells and superoxide production by polymorphonuclear cells and in diluted whole blood were determined before and after the intervention. RESULTS: Cytokine and superoxide production did not differ significantly between hypertriglyceridemic and normolipidemic subjects. alpha-Tocopherol supplementation resulted in a 2- to 3-fold increase in the concentration of alpha-tocopherol in plasma and LDL. Whereas superoxide production in response 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 from that after supplementation. Lipopolysaccharide-induced cytokine production by mononuclear cells decreased after supplementation with alpha-tocopherol. CONCLUSIONS: alpha-Tocopherol differentially influences inflammatory responses of immune cells. These effects of alpha-tocopherol may be relevant in chronic inflammatory processes such as atherogenesis. Copyright © 2000 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]