Jpn. J. Pharmacol. 76 (2), 175-183 (1998)

Effect of Tacrolimus Hydrate (FK506) Ointment on Spontaneous Dermatitis in NC/Nga Mice

Jun Hiroi (1), Takanori Sengoku (1), Kyoko Morita (1), Shinichi Kishi (1), Sachio Sato (1), Toshikazu Ogawa (1), Masaoki Tsudzuki (2), Hiroshi Matsuda (3), Adumi Wada (4) and Kozaburo Esaki (4)

(1) Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 1-6, 2-chome, Kashima, Yodogawa-ku, Osaka 532, Japan
(2) Laboratory of Animal Breeding and Genetics, Faculty of Applied Biological Science, Hiroshima University, Kagamiyama, Higashi Hiroshima 739, Japan
(3) Department of Veterinary Clinic, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183, Japan
(4) Department of Laboratory Animal Science, College of Agriculture, University of Osaka Prefecture, 1-1, Gakuenmachi, Sakai, Osaka 593, Japan

Abstract: The effect of tacrolimus hydrate (FK506) ointment on spontaneous dermatitis in NC/Nga (NC) mice was examined. FK506 ointment (0.1 - 1%) suppressed the development of dermatitis and was also therapeutically effective against established dermatitis. Increases in CD4-positive T cells (helper T cells), mast cells, eosinophils and immunostaining of interleukin (IL)-4, IL-5 and IgE were confirmed in the skin of the NC mice, and FK506 ointment suppressed all of these changes. Increased plasma IgE was also confirmed in the NC mice, and treatment with FK506 ointment reduced the plasma IgE level. These results suggested that FK506 suppressed the dermatitis by inhibiting the activation of inflammatory cells and by blocking the cytokine network in the skin of the NC mice. The commercially available steroid ointments showed only marginal effect on the development of dermatitis and showed some signs of side effects such as alopecia or atrophy of the skin. The effect of the steroids might have been masked by these side effects because the steroids showed similar inhibitory effects on the skin histopathological changes and the increase of plasma IgE. From these results, FK506 ointment can be expected to be a useful drug for atopic dermatitis.

Keywords: FK506, Atopic dermatitis, T cell, Mast cell, Interleukin-4

Copyrightę The Japanese Pharmacological Society 1998

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