Increased susceptibility to systemic candidiasis in interleukin-6 deficient mice

Interleukin-6 (IL-6) is a multifunctional cytokine that regulates multiple aspects of the innate immune response. It has been recently shown that endo genous IL-6 is crucial for an efficient defence against severe infections w ith 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 infec tion with the yeast Candida albicans. During experimental candidemia, IL-6 deficient mice (IL-6-/-) had a decreased survival and an increased fungal l oad in their organs when compared with IL-6+/+ controls, despite increased plasma concentrations of tumour necrosis factor-alpha (TNF), interleukin-1 alpha (IL-1 alpha) and IL-1 beta. IL-6-/- mice were not able to mount an ef ficient neutrophil response during the infection. When mice were rendered n eutropenic by cyclophosphamide, neutropenic IL-6-/- mice were equally susce ptible to C. albicans when compared to neutropenic IL-6+/+ mice, implying t hat neutrophils mediate the beneficial effect of endogenous IL-6. In conclu sion, IL-6-/- mice are more susceptible to disseminated candidiasis, and th e effect of IL-6 is most likely mediated by neutrophils.