Induction of tumor necrosis factor-alpha in murine Candida albicans infection

Candidemia in humans is often associated with an endotoxic shock-like syndrome, comparable to gram-negative sepsis. Tumor necrosis factor-alpha (TNF alpha) has been implicated as a mediator in the endotoxic shock syndrome. The possible role of TNF alpha causing early deaths was explored in a murine model of acute infection with Candida albicans. In vitro data from three mouse strains (BALB/c, C3H/HeJ, and C3H/HeN) and in vivo data from BALB/c mice were obtained. Peritoneal macrophages from all three strains produced TNF alpha in vitro when stimulated with C. albicans. After intravenous infection with 10(8) cfu of C. albicans, mice died within 12 h. TNF concentrations in sera from these mice were significantly greater than in controls. Pretreatment of BALB/c mice with anti-murine TNF alpha did not alter mortality of C. albicans-infected mice, but pretreatment with murine TNF alpha reduced mortality. Therefore, in contrast to what was anticipated, TNF alpha may serve a protective role in murine candidiasis.