Digestive Diseases and Sciences

, Volume 48, Issue 2, pp 408–414 | Cite as

Elimination of Local Macrophages in Intestine Prevents Chronic Colitis in Interleukin-10-Deficient Mice

  • Norihiko Watanabe
  • Koichi Ikuta
  • Kazuichi Okazaki
  • Hiroshi Nakase
  • Yasuhiko Tabata
  • Minoru Matsuura
  • Hiroyuki Tamaki
  • Chiharu Kawanami
  • Tasuku Honjo
  • Tsutomu Chiba


Uncontrolled activation of T cells and macrophages is involved in the development of inflammatory bowel disease (IBD). However, the precise role of intestinal macrophages for development of IBD is till unclear. To investigate the role of local macrophages for development of IBD, we developed poly-D, L-lactic acid microspheres containing dichloromethylene diphosphonate, which was specifically taken up by macrophages and depleted them, and then the animal model for human IBD was treated with this reagent. We have shown that rectal administration of the microspheres reduced the numbers of resident macrophages in the intestinal lymphoid follicles of interleukin-10-deficient mice. Importantly, depletion of intestinal macrophages was associated with suppression of development of chronic colitis. These results suggest that local macrophages in the intestine play a critical role in the development of chronic colitis in an animal model for IBD. Our study implies that elimination of resident macrophages in the intestine may become a therapeutic approach to IBD.

inflammatory bowel disease macrophage drug delivery system microsphere dichloromethylene diphosphonate interleukin 10 


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Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • Norihiko Watanabe
    • 1
  • Koichi Ikuta
    • 2
  • Kazuichi Okazaki
    • 3
  • Hiroshi Nakase
    • 3
  • Yasuhiko Tabata
    • 4
  • Minoru Matsuura
    • 3
  • Hiroyuki Tamaki
    • 3
  • Chiharu Kawanami
    • 3
  • Tasuku Honjo
    • 2
  • Tsutomu Chiba
    • 3
  1. 1.Departments of Gastroenterology and Medical ChemistryGraduate School of Medicine, Kyoto UniversityKyotoJapan
  2. 2.Department of Medical ChemistryGraduate School of Medicine, Kyoto UniversityKyotoJapan
  3. 3.Department of GastroenterologyKyoto UniversityKyotoJapan
  4. 4.Institute for Frontier Medical ScienceKyoto UniversityKyotoJapan

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