The Role of Endogenous Interleukin (IL)–18, IL-12, IL-1b, and Tumor Necrosis Factor–a in the Production of Interferon-g Induced by Candida albicans in Human Whole-Blood Cultures

Despite the importance of interferon (IFN)–g, 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-g synthesis by 72%. Similarly, neutralization of IL-12 or IL-1b by either neutralizing antibodies or IL-1 receptor antagonist also reduced (by 65%) IFNg production. Neutralization of TNF by TNF binding proteins resulted in only a 36% reduction of IFN-g synthesis. In contrast, production of TNF and IL-8 was largely unaffected by these cytokine inhibitors. Thus, C. albicans stimulates IFN-g production in an IL-18– , IL-12– , and IL-1b– 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-1b in patients (e.g., for treatment of autoimmune diseases) may result in increased susceptibility to C. albicans infection.