OMEGA-3 FATTY ACIDS ENHANCE TUMOR NECROSIS FACTOR-α LEVELS IN HEART TRANSPLANT RECIPIENTS


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Abstract

Background.Proinflammatory cytokines may contribute to clinical complications in heart transplant (HTx) recipients. Previous studies have shown immunomodulating effects of omega-3 fatty acids, but the results are somewhat conflicting. In this study, we examined plasma levels of tumor necrosis factor α (TNF-α), interleukin (IL) 10, and their relations to antioxidant vitamins in 45 HTx recipients before and after treatment with omega-3 fatty acids or placebo.Methods.The patients were long-time survivors of heart transplantation, randomized in a double-blind fashion to receive omega-3 fatty acids (3.4 g/day) or placebo for 1 year. Plasma levels of cytokines were measured by enzyme immunoassays and vitamin A, vitamin E, and β-carotene by high-performance liquid chromatography.Results.In the omega-3, but not in the placebo group, there was a rise in the proinflammatory cytokine TNF-α (P <0.05), a decrease in the anti-inflammatory cytokine IL-10 (P =0.07), and a rise in TNF/IL-10 ratio (P <0.05) after 12 months, suggesting a proinflammatory net effect. In the omega-3 group, the increase in TNF-α was associated with an increase in eicosapentaenoic acid in plasma (r =0.58, P <0.02). During omega-3 fatty-acid treatment, but not during placebo, there was a decrease in vitamin E (P <0.05) and β-carotene (P <0.05) levels, and the decrease in vitamin E was inversely correlated with the increase in TNF-α (r =−0.56, P <0.01). The rise in TNF-α levels during omga-3 fatty acids treatment was most pronounced in those patients with transplant coronary artery disease (P <0.04).Conclusion.Our data suggest that omega-3 fatty acids in HTx recipients may change the balance between proinflammatory and anti-inflammatory cytokines in an inflammatory direction, possibly related to prooxidative effects of these fatty acids.

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