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Original Research Communication |
production by peripheral blood mononuclear cells in healthy men is associated with polymorphisms in genes that influence tumor necrosis factor production1,2,3
1 From the Institute of Human Nutrition, School of Medicine, and the Biochemistry and Molecular Biology Division, School of Biological Sciences, University of Southampton, Southampton, United Kingdom (RFG, GO, OM, SH, JME, and PCC), and the Histocompatibility and Immunogenetics Laboratory, Southampton University Hospitals Trust, Southampton, United Kingdom (SJT and WMH).
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.
Key Words: TNF- production • lymphotoxin • genotype • fish oil • inflammation • healthy men • peripheral blood mononuclear cells • TNF*1 • TNF*2 • TNFB*1 • TNFB*2
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