de Oliveira Priscilla Stela Santana, da Paixão Adson Belém Ferreira, da Rocha Junior Laurindo Ferreira, Branco Pinto Duarte Angela Luzia, Pereira Michelly Cristiny, Barreto de Melo Rêgo Moacyr Jesus, da Rocha Pitta Ivan, da Rocha Pitta Maira Galdino
Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Suely-Galdino Therapeutic Innovation Research Center (NUPIT-SG), Federal University of Pernambuco (UFPE), Recife, PE, Brazil.
Rheumatology Service, Clinical Hospital, UFPE, Recife, PE, Brazil.
Immunobiology. 2020 May;225(3):151908. doi: 10.1016/j.imbio.2020.151908. Epub 2020 Jan 30.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint damage, and it may present with comorbidities at the systemic level. The Th1/Th2/Th17 CD4 lymphocyte imbalance produces inflammatory cytokines, which begin to act, injuring joint tissue. Atorvastatin is a cholesterol- lowering drug with a range of biological effects including anti-inflammatory potential. Patients with rheumatoid arthritis who used statins exhibited clinical improvement. However, the mechanism is not fully understood. Therefore, we aimed to evaluate the RA immunomodulatory activity of atorvastatin.
Peripheral blood mononuclear cells (PBMCs) of RA patients and healthy donors were exposed to atorvastatin in different concentrations following a cytotoxicity assay. Th1, Th2, and Th17 cytokines profiles were evaluated in the culture supernatant by cytometric bead array (CBA). Data were analyzed using the Wilcoxon test, and differences were considered significant when p < 0.05.
Atorvastatin showed no toxicity at the tested doses in RA PBMC cultures, and at 10μM, it showed the most significant results, reducing IL-17A (p = 0.002), TNF (p = 0.002), and IL-6 (p = 0.008) supernatant levels. The outcomes also revealed that only patients with more severe disease activity and those sensitive to corticoid treatments were responders to atorvastatin in vitro.
These findings suggest the potential immunomodulatory action of atorvastatin as a mechanism in rheumatoid arthritis treatment.
类风湿性关节炎（RA）是一种以关节损伤为特征的慢性自身免疫性疾病，可能伴有全身性合并症。Th1/Th2/Th17 CD4淋巴细胞失衡会产生炎性细胞因子，这些因子开始发挥作用，损伤关节组织。阿托伐他汀是一种降胆固醇药物，具有一系列生物学效应，包括抗炎潜力。使用他汀类药物的类风湿性关节炎患者表现出临床改善。然而，其机制尚未完全明确。因此，我们旨在评估阿托伐他汀对类风湿性关节炎的免疫调节活性。
在进行细胞毒性试验后，将类风湿性关节炎患者和健康供体的外周血单核细胞（PBMC）暴露于不同浓度的阿托伐他汀中。通过细胞计数珠阵列（CBA）评估培养上清液中Th1、Th2和Th17细胞因子谱。使用Wilcoxon检验分析数据，当p<0.05时，差异被认为具有统计学意义。
在测试剂量下，阿托伐他汀在类风湿性关节炎PBMC培养物中未显示出毒性，在10μM时，其结果最为显著，降低了IL-17A（p = 0.002）、TNF（p = 0.002）和IL-6（p = 0.008）的上清液水平。结果还显示，只有疾病活动更严重的患者和对皮质类固醇治疗敏感的患者在体外对阿托伐他汀有反应。
这些发现表明阿托伐他汀作为类风湿性关节炎治疗机制具有潜在的免疫调节作用。
