Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade.

Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade.
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DOI:
10.1084/jem.20050473
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发表时间:
2005-05-02
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Banchereau J
Banchereau J
中科院分区:
其他
文献类型:
--
作者:
Pascual V;Allantaz F;Arce E;Punaro M;Banchereau J

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全身型幼年特发性关节炎(SoJIA)包括约10%的开始于儿童期的关节炎病例。该疾病在临床表现、关节受累的严重程度和对肿瘤坏死因子阻断缺乏反应方面是独特的。在这里,我们表明,SoJIA患者的血清诱导先天免疫基因的转录,包括白细胞介素(IL)-1在健康的外周血单核细胞(PBMC)。在活化后,SoJIA PBMC释放大量IL-1β。我们给予重组IL-1受体拮抗剂9 SoJIA患者谁是难治性其他疗法。9例患者中有7例获得完全缓解,另外2例患者获得部分缓解。我们的结论是,IL-1是一个主要的介质的炎症级联反应的基础SoJIA,这种细胞因子代表了治疗这种疾病的目标。
Systemic onset juvenile idiopathic arthritis (SoJIA) encompasses ∼10% of cases of arthritis that begin in childhood. The disease is unique in terms of clinical manifestations, severity of joint involvement, and lack of response to tumor necrosis factor blockade. Here, we show that serum from SoJIA patients induces the transcription of innate immunity genes, including interleukin (IL)-1 in healthy peripheral blood mononuclear cells (PBMCs). Upon activation, SoJIA PBMCs release large amounts of IL-1β. We administered recombinant IL-1 receptor antagonist to nine SoJIA patients who were refractory to other therapies. Complete remission was obtained in seven out of nine patients and a partial response was obtained in the other two patients. We conclude that IL-1 is a major mediator of the inflammatory cascade that underlies SoJIA and that this cytokine represents a target for therapy in this disease.
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