Hamid Q, Boguniewicz M, Leung D Y
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
J Clin Invest. 1994 Aug;94(2):870-6. doi: 10.1172/JCI117408.
The mechanisms involved in the initiation and maintenance of skin inflammation in atopic dermatitis (AD) are poorly understood. Recent data suggest that the pattern of cytokines expressed locally plays a critical role in modulating the nature of tissue inflammation. In this study, we used in situ hybridization to investigate the expression of interleukin 4 (IL-4), IL-5, and interferon-gamma (IFN-gamma) messenger RNA (mRNA) in skin biopsies from acute and chronic skin lesions of patients with AD. As compared with normal control skin or uninvolved skin of patients with AD, acute and chronic skin lesions had significantly greater numbers of cells that were positive for mRNA, IL-4 (P < 0.01), and IL-5 (P < 0.01), but not for IFN-gamma mRNA expressing cells. However, as compared with acute AD skin lesions, chronic AD skin lesions had significantly fewer IL-4 mRNA-expressing cells (P < 0.01), but significantly greater IL-5 mRNA (P < 0.01). T cells constituted the majority of IL-5-expressing cells in acute and chronic AD lesions. Chronic lesions also expressed significantly greater numbers of activated EG2+ eosinophils than acute lesions (P < 0.01). These data indicate that although acute and chronic AD lesions are associated with increased activation of IL-4 and IL-5 genes, initiation of acute skin inflammation in AD is associated with a predominance of IL-4 expression whereas maintenance of chronic inflammation is predominantly associated with increased IL-5 expression and eosinophil infiltration.
目前对于特应性皮炎(AD)中皮肤炎症的起始和维持机制了解甚少。近期数据表明,局部表达的细胞因子模式在调节组织炎症性质方面起着关键作用。在本研究中,我们采用原位杂交技术,调查了AD患者急性和慢性皮肤病变皮肤活检组织中白细胞介素4(IL-4)、IL-5和干扰素-γ(IFN-γ)信使核糖核酸(mRNA)的表达情况。与正常对照皮肤或AD患者的未受累皮肤相比,急性和慢性皮肤病变中mRNA、IL-4(P<0.01)和IL-5(P<0.01)阳性的细胞数量显著更多,但IFN-γ mRNA表达细胞的数量并非如此。然而,与急性AD皮肤病变相比,慢性AD皮肤病变中IL-4 mRNA表达细胞显著减少(P<0.01),但IL-5 mRNA显著增多(P<0.01)。在急性和慢性AD病变中,T细胞构成了表达IL-5细胞的大多数。慢性病变中活化的EG2+嗜酸性粒细胞数量也比急性病变显著增多(P<0.01)。这些数据表明,虽然急性和慢性AD病变都与IL-4和IL-5基因的活化增加有关,但AD急性皮肤炎症的起始与IL-4表达占优势有关,而慢性炎症的维持主要与IL-5表达增加和嗜酸性粒细胞浸润有关。