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风湿性疾病中抗白介素-1 治疗的现状。

Actual status of antiinterleukin-1 therapies in rheumatic diseases.

机构信息

Department of Rheumatology and Clinical Immunology, Justus-Liebig-University Giessen, Kerckhoff-Klinik, Bad Nauheim, Germany.

出版信息

Curr Opin Rheumatol. 2010 May;22(3):246-51. doi: 10.1097/BOR.0b013e3283373fa0.

Abstract

PURPOSE OF REVIEW

Several studies have evaluated the efficacy and safety of novel therapeutic options targeting interleukin-1 (IL-1), which not only plays a significant role in rheumatoid arthritis, but also in other rheumatic diseases, for which only limited therapeutical options exist.

RECENT FINDINGS

Three different strategies have been pursued and evaluated in the past years: preventing IL-1 binding by occupying IL-1 receptors with anakinra, an imitation of the naturally occurring IL-1 receptor antagonist, anakinra; development of the fully human monoclonal anti-IL-1beta antibody canakinumab; and synthesis of the dimeric fusion protein rilonacept, consisting of the ligand-binding domain of interleukin-1 receptor type I and its accessory protein, bound to human IgG1. Each of these three anti-IL-1 agents proved efficacy in distinct clinical situations and disease entities.

SUMMARY

Owing to the observation that IL-1 is not only involved in signaling processes resulting in autoimmune and crystal-induced joint destruction but also in several hereditary autoinflammatory syndromes, its value both in pathophysiology as well as for novel advances in medication has significantly improved in the past years leading to an enrichment of the current therapeutic armamentarium for the affected patients.

摘要

目的综述

多项研究评估了靶向白细胞介素-1(IL-1)的新型治疗选择的疗效和安全性,IL-1 不仅在类风湿关节炎中具有重要作用,而且在其他风湿性疾病中也具有重要作用,而这些疾病的治疗选择有限。

最近的发现

过去几年已经采用并评估了三种不同的策略:用 anakinra(一种天然存在的白细胞介素-1 受体拮抗剂的模拟物)占据 IL-1 受体,从而阻止 IL-1 结合;开发全人源单克隆抗 IL-1β 抗体 canakinumab;以及合成二聚体融合蛋白 rilonacept,由白细胞介素-1 受体 I 型的配体结合域及其辅助蛋白与人类 IgG1 结合而成。这三种抗 IL-1 药物中的每一种都在不同的临床情况和疾病实体中证明了疗效。

总结

由于观察到 IL-1 不仅参与导致自身免疫和晶体诱导的关节破坏的信号转导过程,而且还参与几种遗传性自身炎症综合征,因此其在病理生理学以及药物新进展方面的价值在过去几年中得到了显著提高,这使得受影响患者的当前治疗手段更加丰富。

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