A novel benzoimidazole derivative, M50367, modulates helper T type I/II responses in atopic dermatitis mice and intradermal melanoma-bearing mice.
The existence of helper-T cell (Th) subsets, types I and II (Th1/Th2), provides a framework for understanding pathological immune responses. We previously reported that a benzoimidazole derivative, M50367, acted directly on naive Th cells to inhibit their differentiation into Th2 cells. Oral treatment with this compound reduced the Th2 response in vivo and suppressed disease progression in a murine model of atopic asthma. In this study, we investigated the effect of M50367 on 2 other murine disease models, such as atopic dermatitis and intradermal tumor-bearing mice, the pathogenesis of which may be related to the Th2 response. NC/Nga mice treated with a repeated application of picryl chloride developed atopic dermatitis-like skin lesions together with IgE hyper-production. M50367 (30 mg/kg) significantly inhibited the IgE hyper-production without affecting the skin lesions. In C57BL/6 mice bearing intradermal B16F10 melanoma, M50367 (30, 100 mg/kg) significantly inhibited splenomegaly and enhanced spontaneous interferon-gamma release from cultured splenocytes in a dose-dependent manner, though its effect on tumor volume was limited. These results suggest that M50367 could reduce the Th2 response (IgE hyper-production) and enhance the Th1 response (splenocytes interferon-gamma production) in these models. In contrast to previous results in the asthma model, its immunomodulation did not lead to the suppression of disease progression, indicating that the pathogenesis of these models might not simply depend on Th2 response.
Kato
Yutaka
Y
Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan. yutakato@mochida.co.jp
Mizuguchi
Kiyoshi
K
Mochizuki
Hidenori
H
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D003876:Dermatitis, Atopic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008546:Melanoma, Experimental / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D001562:Benzimidazoles; D007155:Immunologic Factors; C119626:M 50367; D007073:Immunoglobulin E