Abstract

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-γ 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 Cε and productive Cε 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-γ 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-γ 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 cellsin vitro and these two immunosuppressors showed higher selectivity toward inhibiting Th1 cell-mediated reactions by limitations in vivo experiments.