IL-6R blockade by chikusetsusaponin IVa butyl ester inhibits Th17 cell differentiation and ameliorates collagen-induced arthritis

Interleukin(IL)-6 is central to the pathogenesis of rheumatoid arthritis(RA).1 IL-6 receptor(IL-6R)blockade is an effective treatment strategy for RA based on the clinical efficacy of tocilizumab.However,serious infections are the most frequent adverse events associated with long-term monotherapy with tocilizumab,an exogenous biomacromolecule.2 Novel small-molecule IL-6R inhibitors with fewer deleterious side effects could therefore have potential as RA treatments.We previously identified chikusetsusaponin IVa butyl ester(CS)as a natural small-molecule IL-6R antagonist.3 Here,we assessed the effects of CS on a mouse model of collagen-induced arthritis(CIA)to evaluate its therapeutic potential against RA.The results showed that CS ameliorated arthritis in CIA mice by inhibiting T-helper 17(Th17)cell differentiation and could serve as a novel agent for treating RA.