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 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-alpha (TNF), interleukin-1 alpha (IL-1 alpha) and IL-1 beta, 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.
van Enckevort
F H
FH
Department of Endocrinology, University Hospital Nijmegen, The Netherlands.
Netea
M G
MG
Hermus
A R
AR
Sweep
C G
CG
Meis
J F
JF
Van der Meer
J W
JW
Kullberg
B J
BJ
D000818:Animals; D002177:Candidiasis / Q000276:immunology*; D004198:Disease Susceptibility; D005260:Female; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha