Mariz Henrique Ataíde, Sato Emília Inoue, Cardoso Pablo Ramon Gualberto, Gonçalves Rafaela, Duarte Angela Luzia Branco Pinto, de Melo Rego Moacyr Jesus Barreto, da Rocha Pitta Ivan, da Rocha Pitta Maíra Galdino
Rheumatology Division, Hospital das Clínicas, Federal University of Pernambuco, Recife, Brazil.
Rheumatology Division, School of Medicine, Federal University of São Paulo, São Paulo, Brazil.
Inflammation. 2023 Apr;46(2):730-738. doi: 10.1007/s10753-022-01768-0. Epub 2022 Dec 2.
Inflammatory T lymphocyte cytokines contribute to tissue damage in SLE patients. Vitamin D (Vit D) has a well-established immunomodulatory action, but few studies have addressed the effect of 1,25 dihydroxyvitamin D3 (1,25 (OH)2D3) on peripheral blood mononuclear cells (PBMCs) in SLE patients. The aim of this study was to evaluate the immnunomodulatory effect of 1,25 (OH)2D3 on T lymphocyte-related cytokines. Blood from 27 female SLE patients was collected for PBMC isolation and anti-DNA, complement, and serum 25 (OH)D3 level measurements. PBMCs were stimulated with anti-CD3/anti-CD28 in the presence or absence of dexamethasone or various concentrations of 1,25 (OH)2D3 for 48 h. We assessed IL-17A, IL-22, IL-21, IL-9, IFN-γ, IL-4, IL-10, IL-2, IL-6, and TNF by cytometric bead assay (CBA) and enzyme immune assay (ELISA) on culture supernatant. The mean age of patients was 36.2 (± 10.5 years) and the median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was 4 (0-6). The addition of 1,25 (OH)2D3 in PBMC culture reduced IL-17 A, IL-22, IL-9, and IFN-γ levels at 100 nM (p ≤ 0.0001). Furthermore, the addition of 1,25 (OH)2D3 at all concentrations increased IL-4 (p ≤ 0.0006), and 0.1 and 1 nM increased IL-10 (p ≤ 0.0004) and 0.1 nM increased IL-2 levels (p ≤ 0.0001). There was no difference regarding IL-21 and TNF levels. The addition of 1,25 (OH)2D3 in PBMC culture presented an inhibitory effect on proinflammatory cytokines and increased immunoregulatory cytokines in SLE patients, suggesting the beneficial effect of this vitamin.
炎性T淋巴细胞细胞因子会导致系统性红斑狼疮（SLE）患者的组织损伤。维生素D（Vit D）具有公认的免疫调节作用，但很少有研究探讨1,25-二羟维生素D3（1,25(OH)2D3）对SLE患者外周血单个核细胞（PBMC）的影响。本研究的目的是评估1,25(OH)2D3对T淋巴细胞相关细胞因子的免疫调节作用。采集27例女性SLE患者的血液，用于分离PBMC并检测抗DNA、补体及血清25(OH)D3水平。在存在或不存在地塞米松或不同浓度的1,25(OH)2D3的情况下，用抗CD3/抗CD28刺激PBMC 48小时。我们通过细胞计数珠分析（CBA）和酶免疫分析（ELISA）检测培养上清液中的白细胞介素-17A（IL-17A）、白细胞介素-22（IL-22）、白细胞介素-21（IL-21）、白细胞介素-9（IL-9）、干扰素-γ（IFN-γ）、白细胞介素-4（IL-4）、白细胞介素-10（IL-10）、白细胞介素-2（IL-2）、白细胞介素-6（IL-6）和肿瘤坏死因子（TNF）。患者的平均年龄为36.2（±10.5岁），系统性红斑狼疮疾病活动指数（SLEDAI）中位数为4（0 - 6）。在PBMC培养中添加1,25(OH)2D3可使100 nM时的IL-17A、IL-22、IL-9和IFN-γ水平降低（p≤0.0001）。此外，添加所有浓度的1,25(OH)2D3均可使IL-4升高（p≤0.0006），0.1 nM和1 nM可使IL-10升高（p≤0.0004），0.1 nM可使IL-2水平升高（p≤0.
