Hospital das Clínicas da Universidade Federal de Pernambuco (UFPE), Av. Prof. Moraes Rego, 1235, Cidade Universitária, Recife, PE, 50670-901, Brazil; Laboratório de Imunomodulação e Novas Abordagens Terapêuticas - Núcleo de Pesquisa em Inovação Terapêutica (LINAT-NUPIT) - UFPE, Av. Prof. Moraes Rego, 1235, Cidade Universitária, Recife, PE, CEP: 50670-901, Brazil.
Laboratório de Imunomodulação e Novas Abordagens Terapêuticas - Núcleo de Pesquisa em Inovação Terapêutica (LINAT-NUPIT) - UFPE, Av. Prof. Moraes Rego, 1235, Cidade Universitária, Recife, PE, CEP: 50670-901, Brazil.
Immunol Lett. 2018 Jun;198:12-16. doi: 10.1016/j.imlet.2018.03.011. Epub 2018 Mar 27.
Immune dysregulation is a central process in the pathogenesis of systemic sclerosis (SSc). Cytokines produced by lymphocytes and monocytes are important mediators and induce tissue damage, recruit additional inflammatory cells, and promote extracellular matrix production and fibrosis. In the present research, we aimed to study the associations between levels of cytokines in serum and culture supernatants from peripheral blood mononuclear cells (PBMCs) and clinical manifestations in SSc patients. Serum samples were obtained from 56 SSc patients and 56 unrelated age- and gender-matched healthy individuals. Resting and anti-CD3/CD28-stimulated PBMC cultures were obtained from 19 SSc patients and 8 healthy controls. IL-2, IL-4, IL-6, IL-10, IL-17A, TNF, and IFN-γ levels were measured by ELISA or CBA. Serum cytokines, except IL-17A, were below the kit detection limit in most of the patients and controls. In unstimulated PBMC, the production of TNF(p = 0.004), IL-10(p = .048), IL-2(p < 0.001), and IL-6 (p = 0.01) was higher in SSc patients than in healthy controls. After anti-CD3/CD28 stimulation, scleroderma PBMCs had lower concentrations of TNF(p = 0.009), IL-10(p = .018), and IL-2(p = .002) than HC. In unstimulated PBMC, IL-2 concentration was higher in patients with esophageal dysmotility (p = 0.04), and IL-10 levels had a positive correlation with modified Rodnan score (p = 0.03). After anti-CD3/CD28 stimulation, higher levels of IL-2 and IL-4 were observed in SSc patients with lung fibrosis (p = 0.01 and 0.006, respectively), and higher levels of IL-10 (p = 0.04) and IL-4 (p = 0.04) in patients with digital ulcers. In conclusion, SSc patients have a different profile of cytokine production and this was associated with clinical manifestations.
免疫失调是系统性硬化症（SSc）发病机制中的一个核心过程。淋巴细胞和单核细胞产生的细胞因子是重要的介质，可诱导组织损伤、募集更多的炎症细胞，并促进细胞外基质的产生和纤维化。在本研究中，我们旨在研究 SSc 患者血清和外周血单个核细胞（PBMC）培养上清液中细胞因子水平与临床表现之间的相关性。从 56 例 SSc 患者和 56 名年龄和性别相匹配的无关健康个体中获得血清样本。从 19 例 SSc 患者和 8 名健康对照中获得静息和抗 CD3/CD28 刺激的 PBMC 培养物。通过 ELISA 或 CBA 测量 IL-2、IL-4、IL-6、IL-10、IL-17A、TNF 和 IFN-γ 水平。在大多数患者和对照中，除 IL-17A 外，血清细胞因子均低于试剂盒检测限。在未刺激的 PBMC 中，SSc 患者的 TNF(p=0.004)、IL-10(p=0.048)、IL-2(p<0.001)和 IL-6(p=0.01)的产生高于健康对照组。在抗 CD3/CD28 刺激后，硬皮病 PBMC 的 TNF(p=0.009)、IL-10(p=0.018)和 IL-2(p=0.002)浓度较低。在未刺激的 PBMC 中，食管运动障碍患者的 IL-2 浓度较高(p=0.04)，而 IL-10 水平与改良 Rodnan 评分呈正相关(p=0.03)。在抗 CD3/CD28 刺激后，肺纤维化患者的 IL-2 和 IL-4 水平升高(p=0.01 和 0.006)，而 IL-10(p=0.04)和 IL-4(p=0.04)水平升高。患有手指溃疡的患者。总之，SSc 患者的细胞因子产生谱不同，这与临床表现有关。
