Abstract
Interleukin (IL)-10 is an anti-inflammatory cytokine that suppresses the T helper 1 immune response and down-regulates macrophages and monocytes. The therapeutic effect of systemic administration of IL-10 for patients with inflammatory bowel disease, however, has not been satisfactory. We examined whether rectal administration of gelatin microspheres (GM) containing IL-10 (GM-IL-10) prevents colitis in IL-10-deficient (IL-10−/−) mice. GM-IL-10 and IL-10 alone were administered rectally. The colon was examined macroscopically and microscopically. IL-12 mRNA expression and CD40 expression in Mac-1-positive cells were also examined. Macroscopic and microscopic examination revealed marked improvement of colitis in IL-10−/− mice treated with GM-IL-10. mRNA expression of IL-12 in Mac-1-positive cells in GM-IL-10-treated mice was significantly decreased compared with that in the mice treated with IL-10 alone. Additionally, CD40 expression in Mac-1-positive cells in GM-IL-10-treated mice was decreased more prominently than in mice treated with IL-10 alone. The therapeutic effects of GM-IL-10 were associated with decreased expression of IL-12 mRNA and down-regulation of CD40 expression in Mac-1-positive cells. GM-IL-10 might be useful for treatment of patients with inflammatory bowel disease.
Footnotes
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Supported by a grant-in-aid for Scientific Research from the Ministry of Culture and Science of Japan (09670543), a grant-in-aid for Research for the Future Program from the Japan Society for the Promotion of Science (JSPS-RFTF 97100201), Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists (03340) and support in research funds from the Japanese Foundation for Research and Promotion of Endoscopy (JFE-1997).
- Abbreviations:
- IBD
- inflammatory bowel disease
- FACS
- flow cytometric cell sorting
- GM
- gelatin microspheres
- IL
- interleukin
- PCR
- polymerase chain reaction
- rmIL-10
- recombinant mouse IL-10
- GM-IL-10
- GM containing rmIL-10
- IL-10−/−
- IL-10-deficient
- Th
- T helper
- PBS
- phosphate-buffered saline
- Received August 21, 2001.
- Accepted December 12, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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