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

Abstract

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-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.