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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics April 2002, 301 (1) 59-65; DOI: https://doi.org/10.1124/jpet.301.1.59
Hiroshi Nakase
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Kazuichi Okazaki
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Yasuhiko Tabata
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Makoto Ozeki
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Norihiko Watanabe
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Masaya Ohana
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Suguru Uose
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Kazushige Uchida
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Toshiki Nishi
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Minoru Mastuura
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Hiroyuki Tamaki
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Toshiyuki Itoh
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Chiharu Kawanami
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Tsutomu Chiba
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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

  • 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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Journal of Pharmacology and Experimental Therapeutics: 301 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 301, Issue 1
1 Apr 2002
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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics April 1, 2002, 301 (1) 59-65; DOI: https://doi.org/10.1124/jpet.301.1.59

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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics April 1, 2002, 301 (1) 59-65; DOI: https://doi.org/10.1124/jpet.301.1.59
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