Role of interleukin-18 in host defense against disseminated Candida albicans infection

Abstract

In mice injected intravenously with Candida albicans, administration of anti-interleukin-18 (IL-18) antibodies increased the yeast load in the kidneys. There was no effect on the organ load with Candida when gamma interferon (IFN-gamma)-deficient mice were treated with anti-IL-18 antibodies, suggesting that the protective effect of IL-18 is mediated through endogenous IFN-gamma.

FIG. 1.

Circulating IL-18 during disseminated candidiasis. Groups of 10 TNF^+/+ LT^+/+ and TNF^−/− LT^−/− mice were injected i.v. with 10⁵ C. albicans CFU. IL-18 concentrations in the serum of TNF^+/+ LT^+/+ (closed circles) and TNF^−/− LT^−/− (open triangles) mice were measured by enhanced chemiluminescence at various time points after infection (the experiment was performed twice, with a total of 10 animals per time point). Asterisk, P < 0.05

FIG. 2.

The role of endogenous IL-18 in the defense against disseminated candidiasis. CBA mice received 200 μl of either NRS (closed circles) or anti-IL-18 antiserum (open triangles) and were thereafter injected i.v. with 10⁵ C. albicans CFU. Outgrowth of the microorganism in the kidneys was assessed on days 1, 3, and 7 after infection in groups of 10 animals. Asterisk, P < 0.05

FIG. 3.

Cytokine concentrations during disseminated candidiasis. CBA mice received 200 μl of either NRS (closed circles) or anti-IL-18 antiserum (open triangles) and were thereafter injected i.v. with 10⁵ C. albicans CFU. Circulating concentrations of IL-1α (A) and IL-6 (B) were measured on days 1, 3, and 7 after infection in subgroups of 10 animals. Asterisk, P < 0.05.