The new water‐soluble artemisinin derivative SM905 ameliorates collagen‐induced arthritis by suppression of inflammatory and Th17 responses

Background and purpose: Our previous study showed that SM905, a novel artemisinin derivative, exhibited potent immunosuppressive activity. In this study, we evaluate preventive and therapeutic effect of SM905 on collagen‐induced arthritis (CIA) in DBA/1 mice, and investigate its mechanisms both in inflammatory and autoimmune aspects of the disease. Experimental approach: CIA was induced by type II bovine collagen (CII) in DBA/1 mice. SM905 was given orally either before (continuously 1 day before booster immunization) or after disease onset (continuously 14 days after booster immunization). Disease incidence and severity were monitored, mRNA expression of proinflammatory mediators was determined by real‐time PCR, purified T cell proliferation was assessed using [ 3 H]‐thymidine incorporated assay, and T helper (Th) 17/Th1/Th2 type cytokine production was examined by ELISA. Key results: Oral treatment with SM905 delayed disease onset, reduced arthritis incidence and severity, and suppressed the enhanced expression of pro‐inflammatory cytokines, chemokines and chemokine receptors in draining lymph nodes. The CII‐induced T cell proliferation and production of interleukin (IL)‐17A by T cells were strikingly inhibited. Correspondingly, the mRNA expression of IL‐17A and RORγt (a specific transcription factor for Th17) was also reduced. This effect was coupled with a striking reduction of IL‐6 production, which has a critical role in Th17 development. In established arthritis, SM905 profoundly inhibited disease progression, reduced IL‐17A and RORγt mRNA expression, and suppressed pro‐inflammatory mediator expression in arthritic joints. Conclusions and implications: SM905 had beneficial effects on CIA by suppressing inflammatory and pathogenic Th17 responses. British Journal of Pharmacology (2008) 153 , 1303–1310; doi: 10.1038/bjp.2008.11 ; published online 11 February 2008