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American Journal of Clinical Nutrition, Vol. 80, No. 5, 1137-1144, November 2004
© 2004 American Society for Clinical Nutrition


ORIGINAL RESEARCH COMMUNICATION

Fish oil and antioxidants alter the composition and function of circulating mononuclear cells in Crohn disease1,2,3

Timothy M Trebble, Nigel K Arden, Stephen A Wootton, Philip C Calder, Mark A Mullee, David R Fine and Mike A Stroud

1 From the Institute of Human Nutrition, School of Medicine (TMT, SAW, PCC, and MAS), the MRC Environmental Epidemiology Unit (NKA), the Medical Statistics/Southampton Statistical Sciences Research Institute (MAM), and the Division of Infection, Inflammation and Repair (DRF), University of Southampton, Southampton, United Kingdom

Background: Crohn disease (CD) is associated with osteoporosis and other extraintestinal manifestations that might be mediated by cytokines from circulating (peripheral blood) mononuclear cells (PBMCs). Fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduces disease activity in patients with CD with raised laboratory markers of inflammation and in healthy subjects alters PBMC function.

Objective: We investigated the effect of fish oil plus antioxidants on cytokine production by PBMCs from patients with CD with raised C-reactive protein concentrations (≥6.9 mg/L) or erythrocyte sedimentation rates (≥18 mm/h).

Design: A randomized placebo-controlled trial of fish oil (2.7 g EPA and DHA/d; n = 31) or placebo (olive oil; n = 31) for 24 wk was conducted in patients with CD. The fish-oil group additionally received an antioxidant preparation (vitamins A, C, and E and selenium). Exclusion criteria included corticosteroid use. Fatty acid composition was measured by gas chromatography. Production of tumor necrosis factor {alpha}, interferon {gamma} (IFN-{gamma}), and prostaglandin E2 (PGE2) was measured by enzyme-linked immunosorbent assays after stimulation with mitogen and endotoxin (lipopolysaccharide).

Results: Fish-oil plus antioxidant dietary supplementation was associated with higher EPA and DHA incorporation into PBMCs (P < 0.001) and lower arachidonic acid (P = 0.006) and lower production of IFN-{gamma} by mitogen-stimulated PBMCs (P = 0.012) and of PGE2 by lipopolysaccharide-stimulated PBMCs (P = 0.047).

Conclusion: Dietary supplementation with fish oil plus antioxidants is associated with modified PBMC composition and lower production of PGE2 and IFN-{gamma} by circulating monocytes or macrophages. The response of extraintestinal manifestations of CD should be investigated in a randomized controlled trial.

Key Words: Mononuclear cell • cytokines • polyunsaturated fatty acids • Crohn disease




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