Effect of Am-80, A Novel Retinoid Derivative, On Contact Hypersensitivity Caused by Repeated Applications of Hapten in Mice

Abstract

Some retinoids show an anti-inflammatory action through regulation of transcription of various genes. In the present study, the inhibitory effect of 4-((5,6,7,8- tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) carbamoyl) benzoic acid (Am-80), a synthetic retinoid, on mouse contact hypersensitivity provoked by repeated applications of 2,4-dinitrofluorobenzene (DNFB) to the ear was investigated. Five-fold applications of DNFB on ears once per week elicited severe contact dermatitis with marked infiltration of inflammatory cells and elevation of anti-dinitrophenyl (DNP)-IgE antibody in the serum. The Am-80 significantly inhibited ear swelling in a dose-dependent manner. In the histopathologic study, infiltration of inflammatory cells was clearly decreased by Am-80. However, Am-80 did not affect the production of DNP-specific IgE antibody both at the transcriptional and post-transcriptional levels. The effects of Am-80 on the transcriptional level of cytokines, interferon (IFN)-γ, interleukin (IL)-1 and IL-4 in cervical lymph nodes were investigated. Marked elevation of mRNA for all cytokines was observed and Am-80 potently inhibited the expression of IFN-γ mRNA, but not IL-1 and IL-4 mRNA. These findings indicated that Am-80 may inhibit the contact dermatitis at the post-sensitization phase by inhibiting IFN-γ production at the transcriptional level in mice.