New cytokine delivery system using gelatin microspheres containing interleukin-10 for experimental inflammatory bowel disease.
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.
Nakase
Hiroshi
H
Division of Gastroenterology and Endoscopic Medicine, Graduate School of Medicine, Kyoto University, Sakyoku, Kyoto, Japan.
Okazaki
Kazuichi
K
Tabata
Yasuhiko
Y
Ozeki
Makoto
M
Watanabe
Norihiko
N
Ohana
Masaya
M
Uose
Suguru
S
Uchida
Kazushige
K
Nishi
Toshiki
T
Mastuura
Minoru
M
Tamaki
Hiroyuki
H
Itoh
Toshiyuki
T
Kawanami
Chiharu
C
Chiba
Tsutomu
T
D000818:Animals; D019013:CD40 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000008:administration & dosage* / Q000633:toxicity*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005079:Excipients; D005260:Female; D005434:Flow Cytometry; D005780:Gelatin; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced* / Q000473:pathology; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity*; D007553:Isotope Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008863:Microspheres; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000378:metabolism
D019013:CD40 Antigens; D016207:Cytokines; D005079:Excipients; D012333:RNA, Messenger; D016753:Interleukin-10; D005780:Gelatin