Therapeutic effects of roxithromycin in interleukin-10-deficient colitis.
BACKGROUND
A limited number of therapeutic strategies are currently available to treat patients with inflammatory bowel disease (IBD). Interleukin-10 (IL-10)-deficient mice, well characterized as an experimental model of IBD, develop severe chronic colitis because of aberrant Th1 responses. Roxithromycin (RXM), a macrolide antibiotic, has received attention because it offers not only antibacterial but also immunosuppressive effects. We examined the immunosuppressive effect of RXM on the development of IBD.


METHODS
To test the efficacy of short-term administration of RXM, elder IL-10-deficient mice (16-20 weeks old) with established colitis were orally treated for 10 days with RXM (20 mg/kg per day). To test the long-term preventive effects of RXM, for 20 weeks young adult IL-10-deficient mice (4-5 weeks old) also were administered RXM orally (20 mg/kg per day).


RESULTS
The short-term treatment-oriented administration of RXM reduced the degree of inflammatory change and lowered serum amyloid A in IL-10-deficient mice with severe colitis. Mononuclear cells from the lamina propria of RXM-treated large intestines showed lower production of IFN-gamma than did those from diseased mice that were untreated. Long-term prevention-oriented administration of RXM suppressed the development of severe colitis and decreased production of IFN-gamma and IL-12. In addition to its expected immunosuppressive effect, RXM treatment also decreased the level of Bacteroides vulgatus, a Gram-negative anaerobe.


CONCLUSIONS
The anti-inflammatory changes observed in IL-10-deficient mice resulted from the efficacy of RXM as an immunosuppressant as well as from its efficacy as an antibiotic. According to our findings, RXM would seem to have significant potential as a preventive and/or therapeutic agent for IBD.
Tamagawa
Hiroshi
H
Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Hiroi
Takachika
T
Mizushima
Tsunekazu
T
Ito
Toshinori
T
Matsuda
Hikaru
H
Kiyono
Hiroshi
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000938:Antigen-Presenting Cells / Q000473:pathology; D003092:Colitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000172:deficiency; D007376:Interleukin-2 / Q000096:biosynthesis; D008197:Lymph Node Excision; D018942:Macrolides / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015575:Roxithromycin / Q000627:therapeutic use*; D000685:Serum Amyloid A Protein / Q000032:analysis; D013154:Spleen
D000900:Anti-Bacterial Agents; D016207:Cytokines; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D018942:Macrolides; D000685:Serum Amyloid A Protein; D016753:Interleukin-10; D015575:Roxithromycin