Igawa K, Yokozeki H, Miyazaki Y, Minatohara K, Satoh T, Katayama I, Nishioka K
Department of Dermatology, Tokyo Medical and Dental University, School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
Clin Exp Allergy. 2001 Mar;31(3):485-94. doi: 10.1046/j.1365-2222.2001.01024.x.
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-1alpha 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-1alpha 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-1alpha was also strongly expressed in the epidermis of the GC-pretreated mice. A subcutaneous injection of anti-IL-1alpha 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-1alpha 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.
在我们的研究中，糖皮质激素（GC）在皮肤上的反复应用增强了过敏性和刺激性接触性皮炎的炎症反应。为了进一步阐明这种接触性超敏反应（CHS）增强的机制，我们研究了在CHS激发部位给予GC后表皮中细胞因子的调节作用。将戊酸倍他米松隔天应用于BALB/c小鼠，共9次。在第12天，用二硝基氟苯（DNFB）对它们进行接触致敏。接下来，在第17天，即最后一次应用GC后的第1天，用DNFB对它们的耳部进行激发。在半抗原激发后切除整个激发的耳垂，然后通过RT-PCR方法进行分析或进行免疫组织化学分析。为了阐明细胞因子在体内的调节作用，用GC预处理的DNFB致敏小鼠注射重组白细胞介素-10（rIL-10）、白细胞介素-1受体拮抗剂（ra）和抗白细胞介素-1α单克隆抗体（mAb），然后用DNFB进行激发。RT-PCR分析表明，在未用GC预处理的小鼠激发皮肤中可检测到白细胞介素-10 mRNA，但在经GC预处理的小鼠激发皮肤中未检测到。另一方面，在经GC预处理的小鼠激发皮肤中，白细胞介素-1α mRNA的表达比未进行GC预处理的小鼠中更强烈地被检测到。此外，激发后的免疫组织化学分析显示，未用GC预处理的小鼠激发表皮中有白细胞介素-10的表达，而在经GC预处理的小鼠中未检测到，白细胞介素-1α在经GC预处理的小鼠表皮中也强烈表达。皮下注射抗白细胞介素-1α单克隆抗体或白细胞介素-1 ra可抑制经GC预处理小鼠中增强的CHS反应。皮下注射rIL-10也可抑制经GC预处理小鼠中CHS反应的增强；然而，在未用GC预处理的小鼠中未观察到这种抑制作用。这些结果表明，在经GC预处理的小鼠激发皮肤部位，表皮中白细胞介素-1α产生的上调和白细胞介素-10产生的抑制似乎在GC诱导的小鼠CHS增强中起关键作用。
