Omega-3 fatty acids enhance tumor necrosis factor-alpha levels in heart transplant recipients

Background. Proinflammatory cytokines may contribute to clinical complicati ons in heart transplant (HTx) recipients. Previous studies have shown immun odulating effects of omega-3 fatty acids, but the results are somewhat conf licting. In this study, we examined plasma levels of tumor necrosis factor alpha (TNF-alpha), 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, ra ndomized in a double-blind fashion to receive omega-3 fatty acids (3.4 g/da y) or placebo for 1 year. Plasma levels of cytokines were measured by enzym e immunoassays and vitamin A, vitamin E, and beta -carotene by high-perform ance liquid chromatography. Results. In the omega-3, but not in the placebo group, there was a rise in the proinflammatory cytokine TNF-alpha (P <0.05), a decrease in the anti-in flammatory 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 g roup, the increase in TNF-alpha was associated with an increase in eicosape ntaenoic acid in plasma (r=0.58, P <0.02). During omega-3 fatty-acid treatm ent, but not during placebo, there was a decrease in vitamin E (P<0.05) and <beta>-carotene (P <0.05) levels, and the decrease in vitamin E was invers ely correlated with the increase in TNF-alpha (r=-0.56, P <0.01). The rise in TNF-alpha 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.