Vol. 283, Issue 1, 321-327, 1997

FK-506 and Cyclosporin A Potentiate the IgE Antibody Production by Contact Sensitization with Hapten in Mice

Hiroichi Nagai, Hidetaka Hiyama, Akihiko Matsuo, Yoshifumi Ueda, Naoki Inagaki and Kenji Kawada

Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502, Japan (H.N., H.H., A.M., Y.U., N.I.) and Gifu College of Medical Technology, 795-1 Nagamine, Ichihiraga, Seki 501-32, Japan (K.K.)

Five repeated topical applications of 2,4-dinitrofluorobenzene to the ears of BALB/c mice resulted in contact dermatitis on the ears as well as significant elevation in dinitrophenol-specific IgE antibody and total IgE in the serum. FK-506 and cyclosporin A inhibited the development of contact dermatitis in terms of skin thickness and histopathological changes of skin lesions. On the contrary, these two drugs potentiated dinitrophenol-specific and total IgE antibody production without affecting IgG and IgM levels in serum. The expression of interferon- mRNA in reverse transcriptase-polymerase chain reaction in the ear was inhibited by FK-506 and cyclosporin A. The expression of interleukin-4 mRNA, germline C and productive C in the auricular lymph node was not affected by these two drugs. Contrary to the above in vivo findings, the immunosuppressors, FK-506 and cyclosporin A, inhibited the production of interferon- and interleukin-2 by cultured Th1 cells (1E10.H2 cells) and of interleukin-4 and -5 by Th2 cells (D10.G4.1 cells) in vitro. These results indicated that FK-506 and cyclosporin A selectively inhibited the Th1 cell-mediated contact dermatitis and potentiated the Th2 cell-mediated IgE antibody production in vivo. This potentiation is probably due to the down-regulation of interferon- production by Th1 cells after the treatment with these drugs. However, because FK-506 and cyclosporin A inhibited the production of cytokines by both Th1 and Th2 cells in vitro and these two immunosuppressors showed higher selectivity toward inhibiting Th1 cell-mediated reactions by limitations in vivo experiments.