Schmitz M K, Botte D A, Sotto M N, Borba E F, Bonfa E, de Mello S B V
Department of Internal Medicine, Rheumatology Division, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
Department of Dermatology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Lupus. 2015 Jul;24(8):854-61. doi: 10.1177/0961203315569335. Epub 2015 Jan 28.
Corticotropin-releasing hormone (CRH) and pro-opiomelanocortin (POMC) axis activation leads to the production of hormones, such as adrenocorticotrophic hormone (ACTH) and the α-melanocyte stimulating hormone (α-MSH). Data regarding the role of these hormones in systemic lupus erythematosus (SLE) are scarce. In the present study we aim to evaluate the participation of this axis in the cutaneous involvement of SLE.
Seventeen SLE patients were clinically evaluated, and biopsies from affected and unaffected skin of these patients were compared with 17 healthy control individuals. Immunohistochemical analyses for CRH, ACTH, α-MSH, and MC-1R were performed, and the serum levels of α-MSH, IL-1, IL-1ra, IL-6, IL-10, IL-12p70, IL-17, TNF-α, and IFN-γ were measured.
The affected skin of the SLE patients exhibited higher CRH expression in the deep dermis compared to the skin of the controls (p = 0.024), whereas the tissue expression of ACTH, cortisol, α-MSH and its receptor MC-1R were comparable in SLE patients and controls. Higher serum levels of IFN-γ (p = 0.041), TNF-α (p = 0.001) and IL-6 (p = 0.049) were observed in SLE patients compared with controls, while α-MSH levels were similar in both groups.
The novel finding of elevated CRH expression solely in the affected skin deep dermis supports the notion of a cutaneous local dysfunction of the CRH-POMC axis in the pathogenesis of cutaneous SLE lesions.
促肾上腺皮质激素释放激素(CRH)和阿片促黑激素原(POMC)轴激活会导致激素的产生,如促肾上腺皮质激素(ACTH)和α-黑素细胞刺激激素(α-MSH)。关于这些激素在系统性红斑狼疮(SLE)中作用的数据很少。在本研究中,我们旨在评估该轴在SLE皮肤受累中的参与情况。
对17例SLE患者进行临床评估,并将这些患者受累和未受累皮肤的活检样本与17名健康对照个体进行比较。进行了CRH、ACTH、α-MSH和MC-1R的免疫组织化学分析,并测量了α-MSH、IL-1、IL-1ra、IL-6、IL-10、IL-12p70、IL-17、TNF-α和IFN-γ的血清水平。
与对照组皮肤相比,SLE患者受累皮肤在真皮深层显示出更高的CRH表达(p = 0.024),而ACTH、皮质醇、α-MSH及其受体MC-1R的组织表达在SLE患者和对照组中相当。与对照组相比,SLE患者中观察到更高的血清IFN-γ水平(p = 0.041)、TNF-α水平(p = 0.001)和IL-6水平(p = 0.049),而两组中的α-MSH水平相似。
仅在受累皮肤真皮深层中CRH表达升高这一新发现支持了CRH-POMC轴在皮肤型SLE病变发病机制中存在皮肤局部功能障碍的观点。