ISSN:
1574-695X
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Biology
,
Medicine
Notes:
We previously demonstrated that interleukin (IL)-12 protected mice against fatal pulmonary infection with a highly virulent strain of Cryptococcus neoformans, which correlated well with the production of interferon (IFN)-γ as well as IL-18 in the primary infected site. In the present study, we examined the role of endogenously synthesized IL-18 in IL-12-induced host resistance to this pathogen. There was little or no production of IFN-γ and IL-18 both at mRNA and protein levels in lungs of mice infected with C. neoformans, while treatment with IL-12 induced a marked production of these cytokines. Caspase-1 mRNA was expressed in infected mice even without IL-12 treatment. Administration of neutralizing anti-IFN-γ monoclonal antibody (mAb) clearly inhibited production of IFN-γ and IL-18 induced by IL-12, while control IgG did not show such an effect. However, administration of IFN-γ did not induce the production of both cytokines in infected mice, although tumor necrosis factor (TNF)-α and IFN-γ-inducible protein (IP)-10 were synthesized by the same treatment. Finally, neutralizing anti-IL-18 antibody (Ab) significantly interfered with the production of IFN-γ and elimination of the microorganism from the lung induced by IL-12 treatment. Furthermore, both IFN-γ synthesis and host protection caused by IL-12 were profoundly diminished in IL-18 gene-disrupted mice. Considered collectively, our results indicated that host protection against C. neoformans induced by IL-12 involved endogenously synthesized IL-18 and that the production of IL-18 was mediated at least in part by endogenous IFN-γ.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1574-695X.2000.tb01430.x
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