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

Louisa Jeffery, Helena Fisk, Philip Calder, Andrew Filer, Karim Raza, Christopher Buckley, Iain McInnes, Peter Taylor, Benjamin Fisher

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)
239 Downloads (Pure)

Abstract

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.
Original languageEnglish
Pages (from-to)748-756
Number of pages9
JournalThe Journal of Rheumatology
Volume44
Issue number6
DOIs
Publication statusPublished - 1 Jun 2017

Keywords

  • Rheumatoid arthritis
  • anti-TNF
  • polyunsaturated fatty acids
  • eicosapentaenoic acid
  • omega-3
  • Th17

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this