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炎性小体与白细胞介素-1β:对炎性疾病治疗的启示

The inflammasome and IL-1β: implications for the treatment of inflammatory diseases.

作者信息

Satoh Takashi, Otsuka Atsushi, Contassot Emmanuel, French Lars E

机构信息

Department of Dermatology, University Hospital Zurich, Zurich 8091, Switzerland.

出版信息

Immunotherapy. 2015;7(3):243-54. doi: 10.2217/imt.14.106.

Abstract

The bioactive form of IL-1β, a key immunoregulatory and proinflammatory cytokine, is produced by the inflammasome - a caspase-1 activating molecular platform - in response to selected danger-associated molecular patterns and pathogen-associated molecular patterns. Advances in understanding the role of IL-1β in inflammatory conditions has resulted in IL-1β becoming a therapeutic target for a number of inflammatory diseases beyond the rare monogenic autoinflammatory diseases characterized by aberrant inflammasome function and enhanced bioactive IL-1β production. In the monogenic autoinflammatory diseases known as cryopyrin-associated periodic syndromes, neutralization of IL-1β results in a rapid and sustained reduction in disease severity without severe side effects, which has consequently driven off-label applications of IL-1β-targeted therapy in other inflammatory diseases. This review summarizes inflammatory diseases for which accumulating evidence suggests a therapeutic potential for IL-1β antagonists.

摘要

白细胞介素-1β(IL-1β)是一种关键的免疫调节和促炎细胞因子,其生物活性形式由炎性小体(一种激活半胱天冬酶-1的分子平台)产生,以响应特定的危险相关分子模式和病原体相关分子模式。对IL-1β在炎症性疾病中作用的理解进展,使得IL-1β成为多种炎症性疾病的治疗靶点,这些疾病不仅仅局限于以炎性小体功能异常和生物活性IL-1β产生增加为特征的罕见单基因自身炎症性疾病。在称为冷吡啉相关周期性综合征的单基因自身炎症性疾病中,中和IL-1β可导致疾病严重程度迅速且持续降低,且无严重副作用,这因此推动了IL-1β靶向治疗在其他炎症性疾病中的非标签应用。本综述总结了越来越多证据表明IL-1β拮抗剂具有治疗潜力的炎症性疾病。

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