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托珠单抗调节类风湿关节炎患者血清脂联素和趋化素水平:IL-6 抑制的潜在心血管保护作用。

Tocilizumab modulates serum levels of adiponectin and chemerin in patients with rheumatoid arthritis: potential cardiovascular protective role of IL-6 inhibition.

机构信息

Rheumatology Unit, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, Siena, Italy.

Rheumatology Unit, S.Giovanni di Dio Hospital, Florence, Italy.

出版信息

Clin Exp Rheumatol. 2019 Mar-Apr;37(2):293-300. Epub 2018 Aug 27.

PMID:30148441
Abstract

OBJECTIVES

Adipokines play an important role in the pathophysiology of rheumatoid arthritis (RA), provide a link between the disease and overweight, contributing to explain the enhanced cardiovascular (CV) risk and influence the response to disease-modifying anti-rheumatic drugs. The aim of this study was to determine the possible effects of intravenous (IV) tocilizumab (TCZ), an interleukin-6 receptor antagonist, on serum levels of leptin, adiponectin, resistin, visfatin, and chemerin.

METHODS

Forty-four RA patients with active disease (DAS28-ESR ≥3.2) were treated with IV TCZ (8 mg/kg) once every 4 weeks for six months: 20 patients received TCZ as monotherapy and 24 in association with methotrexate (MTX). At baseline and monthly, before each infusion, body mass index, DAS28-ESR and Health Assessment Questionnaire (HAQ) were recorded. The laboratory parameters, including the adipokines serum levels were collected at baseline and after six months.

RESULTS

At the end of the follow-up, ESR, CRP, DAS28-ESR and HAQ resulted significantly improved in patients received TCZ as monotherapy or combined with MTX. Lipid profile showed only a significant increase of total cholesterol. A significant reduction of chemerin and an increase of adiponectin were observed in the whole population and in the subgroups of the patients analysed (TCZ mono or combined therapy) without any significant correlations with clinical and biochemical parameters. No changes in the leptin and resistin levels were detected.

CONCLUSIONS

TCZ is able to regulate serum levels of chemerin and adiponectin in RA patients, independently of the disease treatment response, which contributes to explain the CV safety of TCZ.

摘要

目的

脂肪因子在类风湿关节炎(RA)的病理生理学中发挥着重要作用,它将疾病与超重联系起来,有助于解释增强的心血管(CV)风险,并影响疾病修饰抗风湿药物的反应。本研究旨在确定静脉内(IV)托珠单抗(TCZ),一种白细胞介素-6 受体拮抗剂,对瘦素、脂联素、抵抗素、内脏脂肪素和趋化素血清水平的可能影响。

方法

44 例活动期 RA 患者(DAS28-ESR≥3.2)接受 IV TCZ(8mg/kg)治疗,每 4 周一次,持续 6 个月:20 例患者接受 TCZ 单药治疗,24 例患者联合甲氨蝶呤(MTX)治疗。在基线和每月一次,在每次输注前,记录体重指数、DAS28-ESR 和健康评估问卷(HAQ)。在基线和 6 个月后采集实验室参数,包括脂肪因子血清水平。

结果

在随访结束时,接受 TCZ 单药或联合 MTX 治疗的患者的 ESR、CRP、DAS28-ESR 和 HAQ 均显著改善。血脂谱仅显示总胆固醇显著增加。在整个人群和分析的患者亚组(TCZ 单药或联合治疗)中观察到趋化素显著降低和脂联素增加,与临床和生化参数无显著相关性。未检测到瘦素和抵抗素水平的变化。

结论

TCZ 能够调节 RA 患者血清中趋化素和脂联素的水平,而与疾病治疗反应无关,这有助于解释 TCZ 的 CV 安全性。

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