Pétrilli Virginie, Martinon Fabio
Department of Biochemistry, Lausanne University, Lausanne, Switzerland.
Joint Bone Spine. 2007 Dec;74(6):571-6. doi: 10.1016/j.jbspin.2007.04.004. Epub 2007 Aug 21.
IL-1beta is a cytokine with major roles in inflammation and innate immune responses. IL-1beta is produced as an inactive proform that must be cleaved within the cell to generate biologically active IL-1beta. The enzyme caspase-1 catalyzes the reaction. Recent work showed that caspase-1 must be activated by a complex known as the inflammasome. The inflammasome comprises NALP, which is an intracellular receptor involved in innate immunity, and an ASC adapter that ensures caspase-1 recruitment to the receptor. The most extensively described inflammasome to date is formed by the NALP3 receptor within monocytes. Mutations involving the NALP3 gene cause hereditary periodic fever syndromes in humans. Increased inflammasome activity responsible for uncontrolled IL-1beta production occurs in these syndromes. Inhibition of the IL-1beta pathway by IL-1 receptor antagonist (anakinra) is a highly effective treatment for inherited periodic fever syndromes. A major role for inflammasome activity in the development of gout attacks was established recently. Urate monosodium crystals are specifically detected via the NALP3 inflammasome, which results in marked IL-1beta overproduction and initiation of an inflammatory response. This finding opens up new possibilities for the management of gouty attacks.
白细胞介素-1β（IL-1β）是一种在炎症和固有免疫反应中起主要作用的细胞因子。IL-1β以无活性的前体形式产生，必须在细胞内被切割才能生成具有生物活性的IL-1β。半胱天冬酶-1催化该反应。最近的研究表明，半胱天冬酶-1必须被一种称为炎性小体的复合物激活。炎性小体由参与固有免疫的细胞内受体NALP和确保半胱天冬酶-1被招募到该受体的ASC衔接蛋白组成。迄今为止描述最广泛的炎性小体是由单核细胞内的NALP3受体形成的。涉及NALP3基因的突变会导致人类遗传性周期性发热综合征。在这些综合征中会出现炎性小体活性增加，导致IL-1β产生不受控制。白细胞介素-1受体拮抗剂（阿那白滞素）抑制IL-1β途径是治疗遗传性周期性发热综合征的一种非常有效的方法。最近确定了炎性小体活性在痛风发作发展中的主要作用。尿酸单钠晶体通过NALP3炎性小体被特异性检测到，这会导致显著的IL-1β过量产生并引发炎症反应。这一发现为痛风发作的治疗开辟了新的可能性。
