Brief Report: Inhibition of interleukin-6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis
Brief Report: Inhibition of interleukin-6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis
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DOI：
10.1002/art.34477
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发表时间：
2012-08-01
影响因子：
--
通讯作者：
Bonnotte, Bernard
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文献类型：
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作者：
Samson, Maxime;Audia, Sylvain;Bonnotte, Bernard
从免疫学的角度来看，tocilizumab (TCZ)，一种人源化抗白细胞介素-6 （anti - il -6）受体抗体治疗类风湿性关节炎（RA）患者的机制尚不完全清楚。体外研究和小鼠模型研究表明IL-6在Th17细胞分化中起着关键作用。Th17淋巴细胞已被证明在RA发病过程中具有重要作用，本研究旨在探讨IL-6阻断对活动期RA患者Th17细胞和Treg细胞平衡的影响。方法采用风湿病医生开TCZ治疗的活动性RA患者为研究对象。对T细胞群进行表型分析，并评估28个关节的疾病活动评分（DAS28）。第一次输注TCZ （8 mg/kg）前和第三次输注TCZ后测定血清细胞因子水平及其他炎症参数。结果与对照组相比，活动期RA患者外周血中Th17细胞（CD4+IL-17+）水平升高，Treg细胞（CD4+CD25highFoxP3+）水平降低。活动性RA患者循环Treg细胞的抑制功能未受损。在所有患者中，TCZ治疗导致DAS28显著降低，Th17细胞百分比显著降低（中位数从0.9%降至0.45%,P = 0.009）， Treg细胞百分比显著增加（中位数从3.05%降至3.94%,P = 0.0039）。结论本研究首次证实了TCZ对IL-6功能的抑制可以纠正RA患者Th17细胞和Treg细胞之间的失衡。
Objective From an immunologic standpoint, the mechanisms by which treatment with tocilizumab (TCZ), a humanized antiinterleukin-6 (antiIL-6) receptor antibody, results in improvement in rheumatoid arthritis (RA) patients are still not fully understood. In vitro studies and studies in mouse models have demonstrated the critical role of IL-6 in Th17 cell differentiation. Th17 lymphocytes have been shown to be strongly involved in RA pathogenesis, and the purpose of this study was to investigate the effect of IL-6 blockade on the balance between Th17 cells and Treg cells in patients with active RA. Methods Patients with active RA for whom TCZ had been prescribed by a rheumatologist were enrolled in this study. Phenotypic analyses of T cell populations were performed, and the Disease Activity Score in 28 joints (DAS28) was assessed. Serum cytokine levels and other parameters of inflammation were measured before the first infusion and after the third infusion of TCZ (8 mg/kg). Results Compared to controls, levels of Th17 cells (CD4+IL-17+) were increased and Treg cells (CD4+CD25highFoxP3+) were decreased in the peripheral blood of patients with active RA. The suppressive function of circulating Treg cells was not impaired in patients with active RA. TCZ treatment induced a significant decrease in the DAS28 associated with a significant decrease in the percentage of Th17 cells (from a median of 0.9% to 0.45%; P = 0.009) and an increase in the percentage of Treg cells (from a median of 3.05% to 3.94%; P = 0.0039) in all patients. Conclusion This study demonstrates for the first time that inhibition of IL-6 function by TCZ corrects the imbalance between Th17 cells and Treg cells in patients with RA.