Defective IL-10 production in severe phenotypes of Crohn's disease
Defective IL-10 production in severe phenotypes of Crohn's disease
复制标题
DOI：
10.1189/jlb.1108698
复制
发表时间：
2009-05-01
影响因子：
5.5
通讯作者：
Salas, Azucena
中科院分区：
文献类型：
--
作者：
Correa, Ismael;Veny, Marisol;Salas, Azucena
对共生细菌的耐受性丧失被认为是克罗恩病的一种机制。IL-10是一种关键的抗炎细胞因子，在诱导和维持耐受性中起作用。本研究的目的是确定IL-10在克罗恩病患者中对细菌成分的反应，克罗恩病患者根据其表型分为狭窄型、穿透型或炎症型。取克罗恩病患者和健康对照者外周血。在全血培养、分离的CD4（+）细胞和单核细胞来源的树突状细胞（mddc）中测量细胞因子的产生。在非刺激条件下，与炎症性、非穿透性、非狭窄性克罗恩病患者相比，严重表型患者的血培养物中IL-10而非IL-12显著下调。在对LPS的反应中，IL-10在没有瘘管或纤维化的患者中上调更为显著。对分离细胞亚群产生IL-10的研究表明，穿透性克罗恩病的dc细胞，而不是CD4(+) T细胞，在LPS的作用下产生的IL-10显著减少。这些差异与IL-10基因启动子的1082A/G多态性无关。我们在严重形式的克罗恩病患者的全血细胞培养和MDDCs中发现IL-10产生缺陷。一组克罗恩病患者IL-10产生的缺陷可能代表了一种介导该疾病更严重表现的机制。我们建议用IL-10或IL-10诱导疗法治疗可能对这些患者特别有益。j . Leukoc。生物学报。85:896-903；2009.
Loss of tolerance toward commensal bacteria has been invoked as a mechanism for Crohn's disease. IL-10 is a key anti-inflammatory cytokine that plays a role in induction and maintenance of tolerance. The aim of this study is to determine IL-10 production in response to bacterial components in Crohn's disease patients, who were classified according to their phenotypes as stricturing, penetrating, or inflammatory. Peripheral blood was obtained from Crohn's disease patients and healthy controls. Cytokine production was measured in whole blood cultures, isolated CD4(+) cells, and monocyte-derived dendritic cells (MDDCs). Under unstimulated conditions, IL-10, but not IL-12, was down-regulated significantly in blood cultures of patients with severe phenotypes, compared with inflammatory, nonpenetrating, nonstricturing Crohn's disease patients. In response to LPS, IL-10 was up-regulated more significantly in patients with no fistulae or fibrosis. Study of IL-10 production by isolated cell subsets showed that DCs, but not CD4(+) T cells, from penetrating Crohn's disease produced significantly less IL-10 in response to LPS. Differences were not associated with the 1082A/G polymorphism in the IL-10 gene promoter. We show a defect in IL-10 production in whole blood cell cultures and MDDCs in patients with severe forms of Crohn's disease. This defect in IL-10 production by a group of Crohn's disease patients may represent a mechanism mediating more severe manifestations of the disease. We propose that treatment with IL-10 or IL-10-inducing therapies could be of particular benefit to these group of patients. J. Leukoc. Biol. 85: 896-903; 2009.