A possible role of leptin‐associated increase in soluble interleukin‐2 receptor diminishing a clinical response to infliximab in rheumatoid arthritis: Comment on the article by Klaasen et al

Our group has demonstrated that Th17 cells are greatly increased in RA synovial fluid compared to RA and normal peripheral blood (4).Others have shown that the levels of IL-17 and the percentage of Th17 cells in peripheral blood correlate with the 28-joint Disease Activity Score (5) at the onset and during the progression of RA (6).Further, RA patients who receive disease-modifying antirheumatic drugs (DMARDs) plus neutralizing antibody against IL-17 achieve a response according to the American College of Rheumatology 20% improvement criteria (7) more rapidly than do those receiving DMARDs alone (8).As in RA, post-onset treatment with neutralizing antibody to IL-17 reduces the severity of CIA (9).This evidence suggests that IL-17 has important clinical implications in RA as well as in CIA.It has been shown that IL-27 is present in RA synovial fluid and synovial tissue (1,4).However, for IL-27 to effectively suppress Th17 cell differentiation, high levels of this factor are required in the early phase of RA, prior to IL-17 secretion from mature Th17 cells.Consistently, in studies of CIA and AIA (1,2), post-onset treatment with IL-27 did not affect disease progression due to its inability to reduce differentiated Th17 cell numbers.Therefore, use of IL-27 as a therapeutic agent in RA may be limited to patients whose disease is in an early stage and may not be useful in patients with established disease.