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

Abstract

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-gamma) associated with impaired NF-kappaB 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.

• Authors: Masayuki Kohashi, Naozumi Ishimaru, Rieko Arakaki, Yoshio Hayashi
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 58 Issue 2 Pg. 389-400 (Feb 2008) ISSN: 0004-3591 [Print] United States
• PMID: 18240266 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Autoantibodies
• Cytokines
• Immunologic Factors
• Quinolones
• rebamipide
• Alanine

Topics

• Administration, Oral
• Alanine (analogs & derivatives, pharmacology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Autoantibodies (blood)
• Cell Division (drug effects, immunology)
• Cytokines (metabolism)
• Disease Models, Animal
• Female
• Immunologic Factors (pharmacology)
• Lacrimal Apparatus (immunology)
• Mice
• Mice, Mutant Strains
• Quinolones (pharmacology)
• Salivary Glands (immunology)
• Sjogren's Syndrome (drug therapy, immunology)
• T-Lymphocytes (cytology, drug effects, metabolism)
• Thymectomy