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Inflammation Research

, 60:1049 | Cite as

Preventive and therapeutic effects of tacrolimus in an interleukin-10-deficient mouse model of colitis

  • Yohei Okada
  • Noriaki Maeda
  • Shoji Takakura
  • Keiji Miyata
  • Masahiro Koshiba
Original Research Paper

Abstract

Objective

To investigate the preventive and therapeutic effects of tacrolimus on colonic inflammation in interleukin-10-deficient (IL-10−/−) mice, which spontaneously develop T-cell-mediated colitis.

Methods

Tacrolimus or prednisolone, an anti-inflammatory glucocorticoid, was administered to IL-10−/− mice with pre- or post-symptomatic colitis. Effects on colonic inflammation were examined by measuring indices of colitis such as colonic weight/length ratio, cell infiltration, and goblet cell depletion. Effects on cytokine production in colonic lamina propria mononuclear cells (LPMCs) isolated from IL-10−/− mice were also examined.

Results

Tacrolimus prevented development of colitis and improved already-developed colitis. Prednisolone prevented the development of colitis, but had no effect on already-developed colitis. Tacrolimus completely inhibited IFN-γ and TNF-α production of activated T-cells in LPMCs, but only partially inhibited IFN-γ, TNF-α, and IL-12 production of activated monocytes/macrophages in LPMCs. Prednisolone inhibited cytokine production in both cell types but exhibited greater potency on monocytes/macrophages than on T-cells.

Conclusion

These results suggest that the preventive and therapeutic effect of tacrolimus in IL-10−/− mice colitis might be attributed to the inhibition of colonic T-cell activation rather than monocyte/macrophage activation. T-cell immunosuppression may thus be a promising strategy for treating colonic inflammation.

Keywords

Inflammatory bowel disease Tacrolimus Interferon-γ Tumour necrosis factor-α Interleukin-10 

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Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  • Yohei Okada
    • 1
    • 2
  • Noriaki Maeda
    • 1
  • Shoji Takakura
    • 1
  • Keiji Miyata
    • 1
  • Masahiro Koshiba
    • 2
  1. 1.Applied Pharmacology Research Laboratories, Drug Discovery ResearchAstellas PharmaTsukubaJapan
  2. 2.Division of Clinical Laboratory MedicineHyogo College of MedicineNishinomiyaJapan

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