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

The ability of fish oil to suppress tumor necrosis factor alpha production by peripheral blood mononuclear cells in healthy men is associated with polymorphisms in genes that influence tumor necrosis factor alpha production
The ability of fish oil to suppress tumor necrosis factor alpha production by peripheral blood mononuclear cells in healthy men is associated with polymorphisms in genes that influence tumor necrosis factor alpha 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 alpha genes influence TNF-alpha production. Fish oil suppresses TNF-alpha production and has variable antiinflammatory effects on disease. OBJECTIVE: We examined the relation between TNF-alpha and lymphotoxin alpha 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 alpha 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.
tnf-{alpha} production, lymphotoxin {alpha}, genotype, fish oil, inflammation, healthy men, peripheral blood mononuclear cells, tnf*1, tnf*2, tnfb*1, tnfb*2
0002-9165
454-459
Grimble, Robert F.
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Howell, W. Martin
ecbb0dd6-f904-4da2-a05d-e542862531f8
O’Reilly, Gillian
f66a0310-7e33-4ca7-bb85-8e7a0e780a5d
Turner, Stephen J.
e65095fe-e07b-4387-922f-ec6bb9b58800
Markovic, Olivera
e1eae1e1-7002-417b-8468-18819456f7bd
Hirrell, Sharon
61176045-e3b6-4656-bfa5-b66c63a245cb
East, J. Malcolm
9fe7f794-1d89-4935-9a99-b831d786056e
Calder, Philip C.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Grimble, Robert F.
3100e4d2-8f29-4ca6-a95d-38a6a764865f
Howell, W. Martin
ecbb0dd6-f904-4da2-a05d-e542862531f8
O’Reilly, Gillian
f66a0310-7e33-4ca7-bb85-8e7a0e780a5d
Turner, Stephen J.
e65095fe-e07b-4387-922f-ec6bb9b58800
Markovic, Olivera
e1eae1e1-7002-417b-8468-18819456f7bd
Hirrell, Sharon
61176045-e3b6-4656-bfa5-b66c63a245cb
East, J. Malcolm
9fe7f794-1d89-4935-9a99-b831d786056e
Calder, Philip C.
1797e54f-378e-4dcb-80a4-3e30018f07a6

Grimble, Robert F., Howell, W. Martin, O’Reilly, Gillian, Turner, Stephen J., Markovic, Olivera, Hirrell, Sharon, East, J. Malcolm and Calder, Philip C. (2002) The ability of fish oil to suppress tumor necrosis factor alpha production by peripheral blood mononuclear cells in healthy men is associated with polymorphisms in genes that influence tumor necrosis factor alpha production. American Journal of Clinical Nutrition, 76 (2), 454-459.

Record type: Article

Abstract

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 alpha genes influence TNF-alpha production. Fish oil suppresses TNF-alpha production and has variable antiinflammatory effects on disease. OBJECTIVE: We examined the relation between TNF-alpha and lymphotoxin alpha 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 alpha 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.

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Published date: 1 August 2002
Additional Information: Original research communication
Related URLs:
Keywords: tnf-{alpha} production, lymphotoxin {alpha}, genotype, fish oil, inflammation, healthy men, peripheral blood mononuclear cells, tnf*1, tnf*2, tnfb*1, tnfb*2

Identifiers

Local EPrints ID: 25567
URI: http://eprints.soton.ac.uk/id/eprint/25567
ISSN: 0002-9165
PURE UUID: 0916310b-4d85-4ba5-9157-c85a6998eead
ORCID for Philip C. Calder: ORCID iD orcid.org/0000-0002-6038-710X

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Date deposited: 11 Apr 2006
Last modified: 16 Mar 2024 02:51

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Contributors

Author: Robert F. Grimble
Author: W. Martin Howell
Author: Gillian O’Reilly
Author: Stephen J. Turner
Author: Olivera Markovic
Author: Sharon Hirrell
Author: J. Malcolm East
Author: Philip C. Calder ORCID iD

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