Endogenous interleukin (IL)-1 alpha and IL-1 beta are crucial for host defense against disseminated candidiasis.
BACKGROUND
Interleukin (IL)-1 alpha and IL-1 beta are protective proinflammatory cytokines involved in host defense against Candida albicans. It is, however, unknown whether they provide protection through similar mechanisms. We investigated the effect of endogenous IL-1 alpha and IL-1 beta on disseminated C. albicans infection.


METHODS
Mice deficient in the genes encoding IL-1 alpha (IL-1 alpha-/-), IL-1 beta (IL-1 beta-/-), or both molecules (IL-1 alpha-/- beta-/-) were used. Survival and C. albicans outgrowth in the kidneys was assessed after intravenous injection of C. albicans.


RESULTS
Both mortality and C. albicans outgrowth in the kidneys were significantly increased in IL-1 alpha-/- and IL-1 beta-/- mice, compared with those in control mice, with the IL-1 alpha-/- beta-/- mice being most susceptible to disseminated candidiasis. The host defense mechanisms triggered by IL-1 alpha and IL-1 beta differed from one another. IL-1 beta-/- mice showed decreased recruitment of granulocytes in response to an intraperitoneal C. albicans challenge, and generation of superoxide production was diminished in IL-1 beta-/- granulocytes. IL-1 alpha-/- mice had a reduced capacity to damage C. albicans pseudohyphae. Protective type 1 responses were deficient in both IL-1 alpha-/- and IL-1 beta-/- mice, as assessed by production of interferon-gamma by splenocytes in response to heat-killed C. albicans.


CONCLUSIONS
Although IL-1 alpha and IL-1 beta have differential effects on the various arms of host defense, both cytokines are essential for mounting a protective host response against invasive C. albicans infection.
Vonk
Alieke G
AG
Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Netea
Mihai G
MG
van Krieken
Johan H
JH
Iwakura
Yoichiro
Y
van der Meer
Jos W M
JW
Kullberg
Bart Jan
BJ
D000818:Animals; D002176:Candida albicans / Q000276:immunology / Q000472:pathogenicity*; D002177:Candidiasis / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D007121:Immunocompetence / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000276:immunology*; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology
D007375:Interleukin-1; D007371:Interferon-gamma