Background:
Tumor necrosis factor (TNF-) mediates inflammation. High TNF- production has adverse effects during disease. Polymorphisms in the TNF- and lymphotoxin genes influence TNF- production. Fish oil suppresses TNF- production and has variable antiinflammatory effects on disease.

Objective:
We examined the relation between TNF- and lymphotoxin genotypes and the ability of dietary fish oil to suppress TNF- production by peripheral blood mononuclear cells (PBMCs) in healthy men.

Design:
Polymorphisms in the TNF- (TNF*1 and TNF*2) and lymphotoxin (TNFB*1 and TNFB*2) genes were determined in 111 healthy young men. TNF- 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- production. The percentage of subjects in whom fish oil suppressed TNF- production was lowest (22%) in the lowest tertile and doubled with each ascending tertile.
In the highest and lowest tertiles, mean TNF- production decreased by 43% (P < 0.05) and increased by 160% (P < 0.05), respectively. In the lowest tertile of TNF- 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 genotypes among responsive individuals. In the highest tertile, responsiveness to fish oil appeared unrelated to lymphotoxin genotype.

Conclusion:
The ability of fish oil to decrease TNF- production is influenced by inherent TNF- production and by polymorphisms in the TNF- and lymphotoxin genes.