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皮质类固醇抑制系统性硬化症患者趋化因子的产生。

Corticosteroid inhibits chemokines production in systemic sclerosis patients.

作者信息

Dantas Andréa Tavares, de Almeida Anderson Rodrigues, Sampaio Maria Clara Pinheiro Duarte, Cordeiro Marina Ferraz, da Rocha Laurindo Ferreira, de Oliveira Priscilla Stela Santana, Pereira Michelly Cristiny, de Melo Rego Moacyr Jesus Barreto, Marques Claudia Diniz Lopes, da Rocha Pitta Ivan, Duarte Angela Luzia Branco Pinto, da Rocha Pitta Maira Galdino

机构信息

Department of Rheumatology, Hospital das Clínicas da Universidade Federal de Pernambuco, Recife, PE, Brazil; Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica (NUPIT), Universidade Federal de Pernambuco, Recife, PE, Brazil.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica (NUPIT), Universidade Federal de Pernambuco, Recife, PE, Brazil.

出版信息

Steroids. 2017 Nov;127:24-30. doi: 10.1016/j.steroids.2017.08.012. Epub 2017 Sep 1.

Abstract

In this study, we evaluated glucocorticoids (GC) effects on cytokine/chemokine levels in serum samples and peripheral blood mononuclear cell (PBMC) production from systemic sclerosis (SSc) patients. We evaluated cytokine and chemokine levels in serum samples from SSc patients taking or not taking systemic glucocorticoids. PBMCs response to methylprednisolone (MP) was examined from 15 SSc patients and 8 healthy control subjects following PBMC stimulation with anti-CD3/CD28. Cytokine (IFN-γ, TNF, IL-2, IL-4, IL-6, IL-10, and IL-17A) and chemokine (CXCL8/IL-8, CCL5/RANTES, CXCL9/MIG, CCL2/MCP-1, and CXCL10/IP-10) levels were quantified in serum and in PBMC culture supernatants by CBA or ELISA. Compared with patients not taking corticosteroids, we did not observe any significant differences in cytokines/chemokines serum levels in patients using systemic corticosteroids. After stimulation with anti-CD3/CD28, PBMCs treated with MP (100μM), showed a significant reduction of CCL2/MCP-1 (p=0.001), CCL5/RANTES (p=0.04), and CXCL8/IL-8 (p=0.003) levels in SSc patients. In PBMC from healthy controls, we observed decreased IFN-γ, TNF, IL-2, and IL-10 levels after MP treatment, compared with stimulated condition (p<0.01 for all). However in SSc patients, we did not find any significant reduction in these cytokine levels after MP treatment. In conclusion, CCL2/MCP-1, CCL5/RANTES, and CXCL8/IL-8 are chemokines that are potentially modulated by corticosteroids in vitro in SSc patients, but no effect was observed on IL-2, IL-4, IL-6, IL-10, IL-17A, TFN, and IFN-γ secretion. These results suggest a potential effect of GCs on SSc treatment and may reflect the benefit of their use in some patients.

摘要

在本研究中,我们评估了糖皮质激素(GC)对系统性硬化症(SSc)患者血清样本中细胞因子/趋化因子水平以及外周血单核细胞(PBMC)生成的影响。我们评估了正在服用或未服用全身性糖皮质激素的SSc患者血清样本中的细胞因子和趋化因子水平。在用抗CD3/CD28刺激PBMC后,检测了15例SSc患者和8例健康对照受试者的PBMC对甲基泼尼松龙(MP)的反应。通过CBA或ELISA对血清和PBMC培养上清液中的细胞因子(IFN-γ、TNF、IL-2、IL-4、IL-6、IL-10和IL-17A)和趋化因子(CXCL8/IL-8、CCL5/RANTES、CXCL9/MIG、CCL2/MCP-1和CXCL10/IP-10)水平进行定量。与未服用皮质类固醇的患者相比,我们未观察到使用全身性皮质类固醇的患者血清中细胞因子/趋化因子水平有任何显著差异。在用抗CD3/CD28刺激后,用MP(100μM)处理的SSc患者PBMC中,CCL2/MCP-1(p = 0.001)、CCL5/RANTES(p = 0.04)和CXCL8/IL-8(p = 0.003)水平显著降低。在健康对照的PBMC中,与刺激状态相比,MP处理后IFN-γ、TNF、IL-2和IL-10水平降低(所有p<0.01)。然而,在SSc患者中,MP处理后这些细胞因子水平未发现任何显著降低。总之,CCL2/MCP-1、CCL5/RANTES和CXCL8/IL-8是趋化因子,在体外可能受SSc患者皮质类固醇调节,但未观察到对IL-2、IL-4、IL-6、IL-10、IL-17A、TFN和IFN-γ分泌有影响。这些结果提示GC对SSc治疗可能有作用,并且可能反映了其在部分患者中使用的益处。

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