Plasma levels of the n-3 polyunsaturated fatty acid eicosapentaenoic acid are associated with anti-TNF responsiveness in rheumatoid arthritis, and inhibit the etanercept driven rise in Th17 cell differentiation in vitro

Objective
To determine whether levels of plasma n-3 PUFAs are associated with response to anti-TNF agents in RA, and whether this putative effect may have its basis in altering anti-TNF driven Th17 cell differentiation.
Methods
Plasma was collected at baseline and after three months of anti-TNF treatment in 22 patients with established RA, and fatty acid composition of the phosphatidylcholine (PC) component measured. CD4+CD25- T cells and monocytes were purified from the blood of healthy donors and co-cultured in the presence of anti-CD3, with or without etanercept, EPA or the control fatty acid, linoleic acid (LA). Expression of IL-17 and IFNγ was measured by intracellular staining and flow cytometry. 
Results
Plasma PC EPA levels, and the EPA/arachidonic acid ratio, correlated inversely with change in DAS28 scores at 3 months (-0.51; p=0.007, and -0.48; p=0.01 respectively), indicating that higher plasma EPA was associated with a greater reduction in DAS28. Plasma PC EPA was positively associated with EULAR response (P=0.02). An increase in Th17 cells post-therapy has been associated with non-response to anti-TNF. Etanercept increased Th17 frequencies in vitro. Physiological concentrations of EPA, but not LA, prevented this.
Conclusion
EPA status was associated with clinical improvements to anti-TNF therapy in vivo and prevented the effect of etanercept on Th17 cells in vitro. EPA supplementation might be a simple way to improve anti-TNF outcomes in RA patients by suppressing Th17 frequencies.