The ability of fish oil to suppress tumor necrosis factor α production by peripheral blood mononuclear cells in healthy men is associated with polymorphisms in genes that influence tumor necrosis factor α production

Background: Tumor necrosis factor alpha (TNF-alpha) mediates inflammation. High TNF-alpha production has adverse effects during disease. Polymorphisms in the TNF-alpha and lymphotoxin a genes influence TNF-alpha production. Fish oil suppresses TNF-alpha production and has variable anti inflammatory effects on disease. Objective: We examined the relation between TNF-alpha and lymphotoxin a genotypes and the ability of dietary fish oil to suppress TNF-alpha production by peripheral blood mononuclear cells (PBMCs) in healthy men. Design: Polymorphisms in the TNF-alpha (TNF*1 and TNF*2) and lymphotoxin alpha (TNFB*1 and TNFB*2) genes were determined in 111 healthy young men. TNF-alpha production by endotoxin-stimulated PBMCs was measured before and 12 wk after dietary supplementation with fish oil (6 g/d). Results: Homozygosity for TNFB*2 was 2.5 times more frequent in the highest than in the lowest tertile of inherent TNF-alpha production. The percentage of subjects in whom fish oil suppressed TNF-alpha production was lowest (22%) in the lowest tertile and doubled with each ascending tertile. In the highest and lowest tertiles, mean TNF-alpha production decreased by 43% (P < 0.05) and increased by 160% (P < 0.05), respectively. In the lowest tertile of TNF-alpha production, only TNFB*1/TNFB*2 heterozygous subjects were responsive to the suppressive effect of fish oil. In the middle tertile, this genotype was 6 times more frequent than the other lymphotoxin a genotypes among responsive individuals. In the highest tertile, responsiveness to fish oil appeared unrelated to lymphotoxin alpha genotype. Conclusion: The ability of fish oil to decrease TNF-alpha production is influenced by inherent TNF-alpha production and by polymorphisms in the TNF-alpha and lymphotoxin alpha genes.