Increased susceptibility to systemic candidiasis in interleukin-6 deficient mice 1

Interleukin-6 (IL-6) is a multifunctional cytokine that regulates multiple aspects of the innate immune response. It has been recently shown that endogenous IL-6 is crucial for an efficient defence against severe infections with Gram-negative and Gram-positive bacteria. The aim of the present study was to investigate the role of endogenous IL-6 in the defence against infection with the yeast Candida albicans. During experimental candidemia, IL-6 deficient mice (IL-6−/−) had a decreased survival and an increased fungal load in their organs when compared with IL-6+/+ controls, despite increased plasma concentrations of tumour necrosis factor-α (TNF), interleukin-1α (IL-1α) and IL-1β. IL-6−/− mice were not able to mount an efficient neutrophil response during the infection. When mice were rendered neutropenic by cyclophosphamide, neutropenic IL-6−/− mice were equally susceptible to C. albicans when compared to neutropenic IL-6+/+mice, implying that neutrophils mediate the beneficial effect of endogenous IL-6. In conclusion, IL-6−/− mice are more susceptible to disseminated candidiasis, and the effect of IL-6 is most likely mediated by neutrophils.