Effective treatment with oral administration of rebamipide in a mouse model of Sjögren's syndrome

Objective To determine whether oral administration of rebamipide, a mucosal protective agent, is effective in the treatment of Sjögren's syndrome (SS) in the NFS/ sld mouse model of the disease. Methods NFS/ sld mice were given daily oral doses of rebamipide (0.3 mg/kg of body weight or 3 mg/kg) or vehicle alone starting from the age of 4 weeks to the age of 8 weeks. The volume of saliva and tears was monitored during and after treatment. After the final dose, histologic features of the tissues, TUNEL+ apoptotic duct cells in affected glands, T cell and cytokine function, and levels of immunoglobulin isotypes and serum autoantibodies were examined. Results The 3‐mg/kg dose of rebamipide prevented the development of autoimmune lesions. The average volume of saliva in rebamipide‐treated mice was significantly higher than that in control mice. We found decreased TUNEL+ apoptotic duct cells in the salivary and lacrimal glands of rebamipide‐treated mice as compared with control mice. Rebamipide treatment suppressed the activation of CD4+ T cells and Th1 cytokines (interleukin‐2, interferon‐γ) associated with impaired NF‐κB activity. Production of serum autoantibodies, IgM, and IgG1 was clearly inhibited. Conclusion Our findings demonstrate the efficacy of oral administration of rebamipide in the treatment of SS. Rebamipide represents a new therapeutic strategy for the treatment of patients with sicca symptoms caused by SS, as well as for patients with other diseases.