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

Abstract

Background: α-Tocopherol plays an important role in protecting LDL against oxidation. However, additional effects of α-tocopherol at the intracellular level may contribute to the clinical outcome of intervention studies. Objective: We investigated whether α-tocopherol influences the inflammatory responses of immune cells in normolipidemic and hypertriglyceridemic subjects. Design: RRR-α-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 α (TNF-α), interleukin (IL)-1β, 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, α-Tocopherol supplementation resulted in a 2- to 3-fold increase in the concentration of α-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 α-tocopherol supplementation was not significantly different from that after supplementation. Lipopolysaccharide- induced cytokine production by mononuclear cells decreased after supplementation with α-tocopherol. Conclusions: α-Tocopherol differentially influences inflammatory responses of immune cells. These effects of α- tocopherol may be relevant in chronic inflammatory processes such as atherogenesis.