title: FK-506 and cyclosporin A potentiate the IgE antibody production by contact sensitization with hapten in mice.
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-gamma 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 epsilon and productive C epsilon 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-gamma 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-gamma 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.
authors.affiliation: Department of Pharmacology, Gifu Pharmaceutical University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nagai
authors.forename: H
authors.initials: H
authors.lastname: Hiyama
authors.forename: A
authors.initials: A
authors.lastname: Matsuo
authors.forename: Y
authors.initials: Y
authors.lastname: Ueda
authors.forename: N
authors.initials: N
authors.lastname: Inagaki
authors.forename: K
authors.initials: K
authors.lastname: Kawada
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D003877:Dermatitis, Contact / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000276:immunology; D005260:Female; D006241:Haptens / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016559:Tacrolimus / Q000494:pharmacology*; D018417:Th1 Cells / Q000502:physiology
chemical_list: D016207:Cytokines; D006241:Haptens; D007166:Immunosuppressive Agents; D007073:Immunoglobulin E; D016572:Cyclosporine; D004139:Dinitrofluorobenzene; D016559:Tacrolimus