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

• Published in: The American journal of clinical nutrition Vol. 76; no. 2; pp. 454 - 459
• Main Authors: Grimble, Robert F, Howell, W. Martin, O'Reilly, Gillian, Turner, Stephen J, Markovic, Olivera, Hirrell, Sharon, East, J. Malcolm, Calder, Philip C
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Clinical Nutrition 01.08.2002
• Subjects: Adult; adverse effects; anti-inflammatory activity; Biological and medical sciences; dietary supplements; Feeding. Feeding behavior; fish oils; Fish Oils - pharmacology; Fundamental and applied biological sciences. Psychology; genes; Genetics of eukaryotes. Biological and molecular evolution; homozygosity; Human; Humans; inflammation; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; lymphotoxin; Lymphotoxin-alpha - genetics; Male; men; Middle Aged; mononuclear leukocytes; Polymerase Chain Reaction; Polymorphism, Genetic; Population genetics, reproduction patterns; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Human; Monocyte; Cytokine; Biosynthesis; Inflammation; Supplemented diet; Edible oil; Population genetics; Fish oil; Feeding; Animal oil; Tumor necrosis factor α; Polymorphism
• ISSN: 0002-9165
• DOI: 10.1093/ajcn/76.2.454

Background: Tumor necrosis factor α (TNF-α) mediates inflammation. High TNF-α production has adverse effects during disease. Polymorphisms in the TNF-α and lymphotoxin α genes influence TNF-α production. Fish oil suppresses TNF-α production and has variable antiinflammatory effects on disease. Objective: We examined the relation between TNF-α and lymphotoxin α genotypes and the ability of dietary fish oil to suppress TNF-α production by peripheral blood mononuclear cells (PBMCs) in healthy men. Design: Polymorphisms in the TNF-α (TNF*1 and TNF*2) and lymphotoxin α (TNFB*1 and TNFB*2) genes were determined in 111 healthy young men. TNF-α 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-α production. The percentage of subjects in whom fish oil suppressed TNF-α production was lowest (22%) in the lowest tertile and doubled with each ascending tertile. In the highest and lowest tertiles, mean TNF-α production decreased by 43% (P < 0.05) and increased by 160% (P < 0.05), respectively. In the lowest tertile of TNF-α 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 α genotypes among responsive individuals. In the highest tertile, responsiveness to fish oil appeared unrelated to lymphotoxin α genotype. Conclusion: The ability of fish oil to decrease TNF-α production is influenced by inherent TNF-α production and by polymorphisms in the TNF-α and lymphotoxin α genes.