Vol. 301, Issue 1, 59-65, April 2002

New Cytokine Delivery System Using Gelatin Microspheres Containing Interleukin-10 for Experimental Inflammatory Bowel Disease

Hiroshi Nakase, Kazuichi Okazaki, Yasuhiko Tabata, Makoto Ozeki , Norihiko Watanabe, Masaya Ohana, Suguru Uose, Kazushige Uchida, Toshiki Nishi, Minoru Mastuura, Hiroyuki Tamaki, Toshiyuki Itoh, Chiharu Kawanami and Tsutomu Chiba

Division of Gastroenterology and Endoscopic Medicine, Graduate School of Medicine (H.N., K.O., N.W., M.O., S.U., K.U., T.N., M.M., H.T., T.I., C.K., T.C.), and Institute for Frontier Medicine (Y.T., M.O.), Kyoto University, Kyoto, Japan

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.