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.
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(-/-)micecolitis 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.
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Authors: L C Floren; I Bekersky; L Z Benet; Q Mekki; D Dressler; J W Lee; J P Roberts; M F Hebert Journal: Clin Pharmacol Ther Date: 1997-07 Impact factor: 6.875
Authors: S Yamamoto; H Nakase; S Mikami; S Inoue; T Yoshino; Y Takeda; K Kasahara; S Ueno; N Uza; H Kitamura; H Tamaki; M Matsuura; K Inui; T Chiba Journal: Aliment Pharmacol Ther Date: 2008-06-28 Impact factor: 8.171
Authors: Nynke M Kannegieter; Dennis A Hesselink; Marjolein Dieterich; Rens Kraaijeveld; Ajda T Rowshani; Pieter J M Leenen; Carla C Baan Journal: PLoS One Date: 2017-01-25 Impact factor: 3.240