Fish oil and antioxidants alter the composition and function of circulating mononuclear cells in Crohn disease

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 (greater than or equal to6.9 mg/L) or erythrocyte sedimentation rates (greater than or equal to18 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 E-2 (PGE(2)) 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 PGE(2) and IFN-gamma by circulating monocytes or macrophages. The response of extraintestinal manifestations of CD should be investigated in a randomized controlled trial.