Robinson E S, Werth V P
Veteran Affairs Medical Center, Philadelphia, PA, United States; Department of Dermatology, University of Pennsylvania, Philadelphia, PA, United States.
Veteran Affairs Medical Center, Philadelphia, PA, United States; Department of Dermatology, University of Pennsylvania, Philadelphia, PA, United States.
Cytokine. 2015 Jun;73(2):326-34. doi: 10.1016/j.cyto.2015.01.031. Epub 2015 Mar 9.
Cutaneous lupus erythematosus (CLE) is an inflammatory disease with a broad range of cutaneous manifestations that may be accompanied by systemic symptoms. The pathogenesis of CLE is complex, multifactorial and incompletely defined. Below we review the current understanding of the cytokines involved in these processes. Ultraviolet (UV) light plays a central role in the pathogenesis of CLE, triggering keratinocyte apoptosis, transport of nucleoprotein autoantigens to the keratinocyte cell surface and the release of inflammatory cytokines (including interferons (IFNs), tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, IL-8, IL-10 and IL-17). Increased IFN, particularly type I IFN, is central to the development of CLE lesions. In CLE, type I IFN is produced in response to nuclear antigens, immune complexes and UV light. Type I IFN increases leukocyte recruitment to the skin via inflammatory cytokines, chemokines, and adhesion molecules, thereby inducing a cycle of cutaneous inflammation. Increased TNFα in CLE may also cause inflammation. However, decreasing TNFα with an anti-TNFα agent can induce CLE-like lesions. TNFα regulates B cells, increases the production of inflammatory molecules and inhibits the production of IFN-α. An increase in the inflammatory cytokines IL-1, IL-6, IL-10, IL-17 and IL-18 and a decrease in the anti-inflammatory cytokine IL-12 also act to amplify inflammation in CLE. Specific gene mutations may increase the levels of these inflammatory cytokines in some CLE patients. New drugs targeting various aspects of these cytokine pathways are being developed to treat CLE and systemic lupus erythematosus (SLE).
皮肤红斑狼疮（CLE）是一种炎症性疾病，有广泛的皮肤表现，可能伴有全身症状。CLE的发病机制复杂、多因素且尚未完全明确。以下我们综述目前对参与这些过程的细胞因子的认识。紫外线（UV）在CLE的发病机制中起核心作用，引发角质形成细胞凋亡、核蛋白自身抗原转运至角质形成细胞表面以及炎性细胞因子（包括干扰素（IFN）、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1、IL-6、IL-8、IL-10和IL-17）的释放。IFN增加，尤其是I型IFN，是CLE皮损发展的关键。在CLE中，I型IFN是对核抗原、免疫复合物和紫外线的反应而产生的。I型IFN通过炎性细胞因子、趋化因子和黏附分子增加白细胞向皮肤的募集，从而诱导皮肤炎症循环。CLE中TNFα增加也可能导致炎症。然而，用抗TNFα药物降低TNFα可诱发CLE样皮损。TNFα调节B细胞，增加炎性分子的产生并抑制IFN-α的产生。炎性细胞因子IL-1、IL-6、IL-10、IL-17和IL-18增加以及抗炎细胞因子IL-12减少也会加剧CLE中的炎症。特定基因突变可能会使一些CLE患者体内这些炎性细胞因子水平升高。针对这些细胞因子途径各个方面的新药正在研发中，用于治疗CLE和系统性红斑狼疮（SLE）。
