Effect of interleukin‐6 receptor blockade on the balance between regulatory T cells and T helper type 17 cells in rheumatoid arthritis patients

Summary A new paradigm has emerged relating the pathogenesis of rheumatoid arthritis ( RA ), focused on the balance between T helper type 17 cells and regulatory T cells ( T regs ). In humans, both subpopulations depend on transforming growth factor ( TGF) ‐β for their induction, but in the presence of inflammatory cytokines, such as interleukin ( IL) ‐6, the generation of Th 17 is favoured. Tocilizumab is a therapeutic antibody targeting the IL ‐6 receptor ( IL ‐6 R ), which has demonstrated encouraging results in RA . The aim of this study was to evaluate the effect of tocilizumab on Th1 cells, Th 17 cells, IL ‐17 and interferon ( IFN) ‐γ double secretors Th 17/ Th 1 cells, and T regs in RA patients. Eight RA patients received tocilizumab monthly for 24 weeks and blood samples were obtained every 8 weeks to study T cell populations by flow cytometry. The frequency of Th 17 cells, Th 1 cells and Th 17/ Th 1 cells was evaluated in peripheral blood mononuclear cells ( PBMCs ) activated in vitro with a polyclonal stimulus. T regs were identified by their expression of forkhead box protein 3 ( F oxP3) and CD 25 by direct staining of PBMCs . Although no changes were detected in the frequency of Th 1 or Th 17 cells, the percentages of peripheral T regs increased after therapy. In addition, the infrequent Th 17/ Th 1 subpopulation showed a significant increment in tocilizumab‐treated patients. In conclusion, tocilizumab was able to skew the balance between Th 17 cells and T regs towards a more protective status, which may contribute to the clinical improvement observed in RA patients.