Levels of Transforming Growth Factor-β Are Low in Systemic Lupus Erythematosus Patients with Active Disease
Levels of Transforming Growth Factor-β Are Low in Systemic Lupus Erythematosus Patients with Active Disease
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DOI：
10.3899/jrheum.100180
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发表时间：
2010-10-01
影响因子：
3.9
通讯作者：
Nossent, Johannes C.
中科院分区：
文献类型：
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作者：
Becker-Merok, Andrea;Eilertsen, Gro Ostli;Nossent, Johannes C.
Objective.细胞因子是免疫反应的中心调节因子，但系统性红斑狼疮（SLE）中这一复杂网络的工作机制尚未完全了解。我们研究了一系列炎症和免疫调节细胞因子，以确定其作为SLE疾病亚群生物标志物的价值。这是一项在102例SLE患者中进行的横断面研究（87%为女性，病程10.6年）。白细胞介素1 β的循环浓度（IL-1 β）、IL-4、IL-6、IL- 10、IL-12、IL-17、单核细胞趋化蛋白1（MCP-1）、巨噬细胞炎性蛋白I（MIP-1 α）、MIP-1 β、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）和总转化生长因子-β 1（TGF-β 1）与疾病活动有关SLE疾病活动指数（SLEDAI）、淋巴细胞亚群、自身抗体水平、累积损伤（系统性狼疮国际合作临床/ACR损伤指数（SDI））和伴随治疗。与对照组相比，SLE患者的TGF-β 1（p = 0.01）和IL-1 β（p = 0.0004）水平较低。SLEDAI评分为1-10且SDI > 3的患者的TGF-β 1水平较低;并且与CD 4+、CD 8+和自然杀伤细胞计数相关;并且与类固醇或细胞毒性药物的使用无关。心血管药物治疗与较低的IL-12水平相关。研究的其他细胞因子与疾病之间不存在一致的相关性。较低的TGF-β 1是SLE患者中最一致的细胞因子异常。与疾病活动性、淋巴细胞亚群和损伤的相关性表明，TGF-β 1可能是SLE的治疗靶点。（2010年8月1日首次发布; J Rheumol 2010;37：2039-45; doi：10.3899/jrheum.100180）
Objective. Cytokines are central regulators of the immune response but the workings of this complex network in systemic lupus erythematosus (SLE) are not fully understood. We investigated a range of inflammatory and immune-modulating cytokines to determine their value as biomarkers for disease subsets in SLE.Methods. This was a cross-sectional study in 102 patients with SLE (87% women, disease duration 10.6 yrs). Circulating concentrations of interleukin 1 beta (IL-1 beta), IL-4, IL-6, IL- 10, IL-12, IL-17, monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein I (MIP-1 alpha), MIP-1 beta, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and total transforming growth factor-beta 1 (TGF-beta 1) were related to disease activity (SLE Disease Activity Index; SLEDAI), lymphocyte subsets, autoantibody levels, accrued damage (Systemic Lupus International Collaborating Clinics/ACR Damage Index; SDI), and concomitant treatment.Results. Patients with SLE had lower levels of TGF-beta 1 (p = 0.01) and IL-1 beta (p = 0.0004) compared to controls. TGF-beta 1 levels were lower in patients with SLEDAI scores 1-10 and SDI > 3; and were correlated with CD4+, CD8+, and natural killer cell counts; and were independent of steroid or cytotoxic drug use. Treatment with cardiovascular drugs was associated with lower IL-12 levels. No consistent disease associations existed for the other cytokines investigated.Conclusion. Lower TGF-beta 1 was the most consistent cytokine abnormality in patients with SLE. The associations with disease activity, lymphocyte subsets, and damage suggest that TGF-beta 1 may be a therapeutic target of interest in SLE. (First Release August 1 2010; J Rheumatol 2010;37:2039-45; doi:10.3899/jrheum.100180)