The role of endogenous interleukin (IL)-18, IL-12, IL-1β, and tumor necrosis factor-α in the production of interferon-γ induced by Candida albicans in human whole-blood cultures
The role of endogenous interleukin (IL)-18, IL-12, IL-1β, and tumor necrosis factor-α in the production of interferon-γ induced by Candida albicans in human whole-blood cultures
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DOI：
10.1086/339410
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发表时间：
2002-04-01
影响因子：
6.4
通讯作者：
Dinarello, CA
中科院分区：
文献类型：
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作者：
Netea, MG;Stuyt, RJL;Dinarello, CA
尽管干扰素（IFN）-γ、肿瘤坏死因子（TNF）和白细胞介素（IL）-18对于宿主防御念珠菌病的重要性，但导致它们被白色念珠菌刺激的途径尚不清楚。在全血模型中，IL-18结合蛋白对IL-18的中和作用降低了C。白念珠菌诱导的IFN-γ合成减少72%。类似地，中和抗体或IL-1受体拮抗剂对IL-12或IL-1 β的中和作用也降低了IFN-γ的产生（65%）。TNF结合蛋白中和TNF导致IFN-γ合成仅减少36%。相反，TNF和IL-8的产生在很大程度上不受这些细胞因子抑制剂的影响。因此，白色念珠菌以IL-18、IL-12和IL-1 β依赖性方式刺激IFN-γ产生，而TNF和IL-8的产生不依赖于这些细胞因子。阻断患者中IL-18、IL-12和IL-1 β的生物活性（例如，用于治疗自身免疫性疾病）可能导致对白色念珠菌感染的易感性增加。
Despite the importance of interferon (IFN)-gamma, tumor necrosis factor (TNF), and interleukin (IL)-18 for host defense against candidiasis, the pathways leading to their stimulation by Candida albicans are unclear. In a whole-blood model, IL-18 neutralization by IL-18 binding protein decreased C. albicans-induced IFN-gamma synthesis by 72%. Similarly, neutralization of IL-12 or IL-1beta by either neutralizing antibodies or IL-1 receptor antagonist also reduced (by 65%) IFN-gamma production. Neutralization of TNF by TNF binding proteins resulted in only a 36% reduction of IFN-gamma synthesis. In contrast, production of TNF and IL-8 was largely unaffected by these cytokine inhibitors. Thus, C albicans stimulates IFN-gamma production in an IL-18-, IL-12-, and IL-1beta-dependent manner, whereas production of TNF and IL-8 is independent of these cytokines. Blocking the biologic activities of IL-18, IL-12, and IL-1beta in patients (e.g., for treatment of autoimmune diseases) may result in increased susceptibility to C albicans infection.