The anti-spasticity drug baclofen alleviates collagen-induced arthritis and regulates dendritic cells

Baclofen is used clinically as a drug that treats spasticity, which is a syndrome characterized by excessive contraction of the muscles and hyperflexia in the central nervous system (CNS), by activating GABAB receptors (GABABRs). Baclofen was recently reported to desensitize chemokine receptors and to suppress inflammation through the activation of GABABRs. GABABRs are expressed in various immune cells, but the functions of these receptors in autoimmune diseases remain largely unknown. In this study, we investigated the effects of baclofen in murine collagen-induced arthritis (CIA). Oral administration of baclofen alleviated the clinical development of CIA, with a reduced number of IL-17-producing T helper 17 (TH17) cells. In addition, baclofen treatment suppressed dendritic cell (DC)-primed TH17 cell differentiation by reducing the production of IL-6 by DCs in vitro. Furthermore, the pharmacological and genetic blockade of GABABRs in DCs weakened the effects of baclofen, indicating that GABABRs are the molecular targets of baclofen on DCs. Thus, our findings revealed a potential role for baclofen in the treatment of CIA, as well as a previously unknown signaling pathway that regulates DC function. J. Cell. Physiol. 230: 1438–1447, 2015. © 2015 Wiley Periodicals, Inc., A Wiley Company