Topical glucocorticoids application induced an augmentation in the expression of IL-1 alpha while inhibiting the expression of IL-10 in the epidermisin murine contact hypersensitivity

Background The repeated application of glucocorticoids (GC) on the skin aug mented the inflammatory response of both allergic and irritant contact derm atitis in our studies. Objective In order to further clarify the mechanism of such an augmentation of contact hypersensitivity (CHS), we investigated the modulatory effects of cytokines in the epidermis after the administration of GC at challenged sites in CHS. Methods Diflucortolone valerate was applied to BALB/c mice on alternate day s for a total of nine times. On day 12, they were contact sensitized with d initrofluorobenzene (DNFB). Next, on day 17, one day after the last applica tion of GC, they were challenged with DNFB on the ear. The whole challenged ear lobes were removed after a hapten challenge and then were analysed by the RT-PCR method or underwent an immunohistochemical analysis. To clarify the modulatory effects of cytokines in vivo, DNFB sensitized mice pre-treat ed with GC were injected with rIL-10, IL-1 receptor antagonist (ra) and ant i-IL-1 alpha monoclonal antibody (mAb) and thereafter were challenged with DNFB. Results A RT-PCR analysis has demonstrated IL-10 mRNA to be detected in the challenged skin of non-GC-pretreated mice but not in that of GC-pre-treate d mice after challenge. On the other hand, the expression of IL-1 alpha mRN A in the challenged skin of mice pretreated with GC was more strongly detec ted that that in mice without GC-pretreatment. Furthermore, an immuno-histo chemical analysis in the challenge showed the expression of IL-10 in the sk in showed the expression of IL-10 in the challenged epidermis of the non-GC -pretreated mice but not in the GC-pretreated mice and IL-1 alpha was also strongly expressed in the epidermis of the GC-pretreated mice. A subcutaneo us injection of anti-IL-1 alpha mAb or IL-1 ra inhibited the augmented CHS reaction in the GC-pretreated mice. A subcutaneous injection of rIL-10 also inhibited the augmentation of the CHS reaction in the GC-pretreated mice; however, no such inhibition was observed in the non-GC-pretreated mice. Conclusion These results indicated that both an up-regulation of IL-1 alpha production and the inhibition of the IL-10 production in the epidermis at the challenged skin sites in the GC-pretreated mice appear to play a critic al role in the GC-induced augmentation of murine CHS.