Yawalkar N, Karlen S, Egli F, Brand C U, Graber H U, Pichler W J, Braathen L R
Dermatological Clinic and the Clinic for Rheumatology and Clinical Immunology/Allergology, Department of Clinical Research, Inselspital, University of Bern, Bern, Switzerland.
J Allergy Clin Immunol. 2000 Nov;106(5):941-7. doi: 10.1067/mai.2000.109825.
Previous reports indicate that IL-12 may be involved in the development of chronic atopic dermatitis. However, the cellular source of this cytokine in the skin and its expression during successful treatment of the skin lesions are not known.
Our purpose was to delineate the precise in situ localization of IL-12 and its modulation under topical treatment with corticosteroids.
Skin biopsy specimens were obtained from nonlesional, lesional, and treated skin of patients with atopic dermatitis and from healthy skin of nonatopic control subjects. IL-12 was investigated by real-time quantitative reverse transcriptase-PCR and immunohistochemistry.
Expression of IL-12 p40 mRNA was significantly enhanced in lesional skin from atopic dermatitis and strongly down-regulated after treatment with topical corticosteroids for 9 to 10 days. In contrast, similar levels of IL-12 p35 transcripts were found in all the samples without any significant differences after treatment. In addition, a strong enhancement of IL-12 immunoreactivity was observed on the mononuclear cell infiltrate in the lesional skin samples, which was also markedly reduced after treatment. IL-12 immunoreactivity was mainly located in the cytoplasm of dermal dendritic cells and macrophages as well as some Langerhans cells.
Our data suggest that the enhanced local production of IL-12 in dendritic cells and macrophages may be responsible for up-regulating production of IFN-gamma in chronic lesions and strengthen the idea that IL-12 may have a pivotal role in promoting inflammation in atopic dermatitis.
既往报道表明，白细胞介素-12（IL-12）可能参与慢性特应性皮炎的发病过程。然而，这种细胞因子在皮肤中的细胞来源及其在皮损成功治疗期间的表达情况尚不清楚。
我们的目的是明确IL-12的精确原位定位及其在局部应用皮质类固醇治疗下的调节情况。
从特应性皮炎患者的非皮损、皮损及治疗后的皮肤以及非特应性对照受试者的健康皮肤获取皮肤活检标本。通过实时定量逆转录聚合酶链反应和免疫组织化学研究IL-12。
IL-12 p40 mRNA在特应性皮炎的皮损皮肤中表达显著增强，在局部应用皮质类固醇治疗9至10天后强烈下调。相比之下，在所有样本中发现IL-12 p35转录本水平相似，治疗后无任何显著差异。此外，在皮损皮肤样本的单核细胞浸润上观察到IL-12免疫反应性强烈增强，治疗后也明显降低。IL-12免疫反应性主要位于真皮树突状细胞、巨噬细胞以及一些朗格汉斯细胞的细胞质中。
我们的数据表明，树突状细胞和巨噬细胞中IL-12局部产生的增强可能是慢性皮损中γ干扰素产生上调的原因，并强化了IL-12可能在促进特应性皮炎炎症中起关键作用的观点。
