Digestive Diseases and Sciences

, Volume 48, Issue 2, pp 408–414

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


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

DOI: 10.1023/A:1021960401290

Cite this article as:
Watanabe, N., Ikuta, K., Okazaki, K. et al. Dig Dis Sci (2003) 48: 408. doi:10.1023/A:1021960401290


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 diseasemacrophagedrug delivery systemmicrospheredichloromethylene diphosphonateinterleukin 10

Copyright information

© Plenum Publishing Corporation 2003