The Role of Endogenous Interleukin (IL)–18, IL‐12, IL‐1β, and Tumor Necrosis Factor–α in the Production of Interferon‐γ Induced byCandida albicansin Human Whole‐Blood Cultures
Despite the importance of interferon (IFN)-γ, 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-γ synthesis by 72%. Similarly, neutralization of IL-12 or IL-1β by either neutralizing antibodies or IL-1 receptor antagonist also reduced (by 65%) IFN-γ production. Neutralization of TNF by TNF binding proteins resulted in only a 36% reduction of IFN-γ synthesis. In contrast, production of TNF and IL-8 was largely unaffected by these cytokine inhibitors. Thus, C. albicans stimulates IFN-γ production in an IL-18-, IL-12-, and IL-1β-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-1β in patients (e.g., for treatment of autoimmune diseases) may result in increased susceptibility to C. albicans infection.