Plasma Levels of Eicosapentaenoic Acid Are Associated with Anti-TNF Responsiveness in Rheumatoid Arthritis and Inhibit the Etanercept-driven Rise in Th17 Cell Differentiationin Vitro

Abstract

ObjectiveTo 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 MethodsPlasma was collected at baseline and after three months of anti-TNF treatment in ResultsPlasma 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 EPA and anti-TNF response 2 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. ConclusionEPA 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.

High erythrocyte levels of the n-6 polyunsaturated fatty acid linoleic acid are associated with lower risk of subsequent rheumatoid arthritis in a southern European nested case–control study

“…This was thought to be reverse causation, with a metabolic state in RA driving increased desaturase enzyme activity for which LA is a substrate. Indeed, we have previously suggested that D5D activity may be reduced following treatment with anti-TNF 38. In this cohort we did not find D5D or D6D product to precursor ratios to be associated with risk of RA, or to vary with time to diagnosis, but we did observe a non-statistically significant trend for lower LA levels in subjects closest in time to RA diagnosis.…”

The role of diet in rheumatoid arthritis

“…Additionally, a relationship between serum EPA levels and good treatment response, as defined by EULAR, was found ( p = 0.02). It may be explained by the fact that while Th17 stimulation was found both to be exaggerated by etanercept in vitro and also to be present in patients with a poor treatment response, EPA intake seems to prevent it [ 21 ].…”

Could Omega 3 Fatty Acids Preserve Muscle Health in Rheumatoid Arthritis?

“…It improved also the remission when associated to conventional disease-modifying DMARDs [98]. In addition, the concentration of EPA in serum was associated with a better response to anti-TNF therapy [99]. Taken together, these results suggested that omega 3 FA have a favorable effect on inflammation and pain in RA, that can be, at least partially, explained by the generation of omega 3 derived lipid mediators [100,101].…”