caa a22 4500 445886137 CHVBK 20180317145600.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s00011-011-0366-x doi (NATIONALLICENCE)springer-10.1007/s00011-011-0366-x Preventive and therapeutic effects of tacrolimus in an interleukin-10-deficient mouse model of colitis [Elektronische Daten] [Yohei Okada, Noriaki Maeda, Shoji Takakura, Keiji Miyata, Masahiro Koshiba] 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. Springer Basel AG, 2011 Inflammatory bowel disease nationallicence Tacrolimus nationallicence Interferon-γ nationallicence Tumour necrosis factor-α nationallicence Interleukin-10 nationallicence Okada Yohei Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma, 21, Miyukigaoka, 305-8585, Tsukuba, Ibaraki, Japan aut Maeda Noriaki Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma, 21, Miyukigaoka, 305-8585, Tsukuba, Ibaraki, Japan aut Takakura Shoji Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma, 21, Miyukigaoka, 305-8585, Tsukuba, Ibaraki, Japan aut Miyata Keiji Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma, 21, Miyukigaoka, 305-8585, Tsukuba, Ibaraki, Japan aut Koshiba Masahiro Division of Clinical Laboratory Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, 663-8501, Nishinomiya, Hyogo, Japan aut Inflammation Research SP Birkhäuser Verlag Basel 60/11(2011-11-01), 1049-1059 1023-3830 60:11<1049 2011 60 11 https://doi.org/10.1007/s00011-011-0366-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00011-011-0366-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Okada Yohei Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma, 21, Miyukigaoka, 305-8585, Tsukuba, Ibaraki, Japan aut NATIONALLICENCE 700 1- Maeda Noriaki Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma, 21, Miyukigaoka, 305-8585, Tsukuba, Ibaraki, Japan aut NATIONALLICENCE 700 1- Takakura Shoji Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma, 21, Miyukigaoka, 305-8585, Tsukuba, Ibaraki, Japan aut NATIONALLICENCE 700 1- Miyata Keiji Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma, 21, Miyukigaoka, 305-8585, Tsukuba, Ibaraki, Japan aut NATIONALLICENCE 700 1- Koshiba Masahiro Division of Clinical Laboratory Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, 663-8501, Nishinomiya, Hyogo, Japan aut NATIONALLICENCE 773 0- Inflammation Research SP Birkhäuser Verlag Basel 60/11(2011-11-01), 1049-1059 1023-3830 60:11<1049 2011 60 11 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer