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-gamma) associated with impaired NF-kappaB activity. Production of serum autoantibodies, IgM, and IgG1 was clearly inhibited.


CONCLUSIONS
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.
Kohashi
Masayuki
M
University of Tokushima Graduate School, Tokushima, Japan.
Ishimaru
Naozumi
N
Arakaki
Rieko
R
Hayashi
Yoshio
Y
D000284:Administration, Oral; D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001323:Autoantibodies / Q000097:blood; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology; D007765:Lacrimal Apparatus / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D015363:Quinolones / Q000494:pharmacology*; D012469:Salivary Glands / Q000276:immunology; D012859:Sjogren's Syndrome / Q000188:drug therapy* / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013934:Thymectomy
D000893:Anti-Inflammatory Agents; D001323:Autoantibodies; D016207:Cytokines; D007155:Immunologic Factors; D015363:Quinolones; C052785:rebamipide; D000409:Alanine