ISSN:
1365-2222
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
The repeated application of glucocorticoids (GC) on the skin augmented the inflammatory response of both allergic and irritant contact dermatitis in our studies.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.Diflucortolone valerate was applied to BALB/c mice on alternate days for a total of nine times. On day 12, they were contact sensitized with dinitrofluorobenzene (DNFB). Next, on day 17, one day after the last application 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-treated with GC were injected with rIL-10, IL-1 receptor antagonist (ra) and anti-IL-1α monoclonal antibody (mAb) and thereafter were challenged with DNFB.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-treated mice after challenge. On the other hand, the expression of IL-1α mRNA in the challenged skin of mice pretreated with GC was more strongly detected that that in mice without GC-pretreatment. Furthermore, an immuno-histochemical analysis in the challenge showed the expression of IL-10 in the skin 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-1α was also strongly expressed in the epidermis of the GC-pretreated mice. A subcutaneous injection of anti-IL-1α 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.These results indicated that both an up-regulation of IL-1α 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 critical role in the GC-induced augmentation of murine CHS.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1046/j.1365-2222.2001.01024.x
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