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