Reduced host resistance and Th1 response to Cryptococcus neoformans in interleukin-18 deficient mice

Using interleukin (IL)-18 deficient (IL-18(-/-)) mice, we examined the role of IL-18 in the host resistance and Th1 response against infection with Cr yptococcus neoformans. Fungal clearance in the lung was reduced in IL-18(-/ -) mice, although there was no significant change in the level of dissemina tion to the brain. The DTH response, as determined by footpad swelling, was also diminished in IL-18(-/-) mice compared to control wild-type (WT) mice . The levels of IL-12 and interferon (IFN)-gamma in the sera were significa ntly lower in IL-18(-/-) mice than in WT mice. Spleen cells from infected W T mice produced a high level of IFN-gamma upon stimulation with the microbe , while only a low level of IFN-gamma production was detected in spleen cel ls from infected IL-18(-/-) mice; Administration of IL-18 almost completely restored the reduced response in IL-18(-/-) mice, while IL-12 showed a mar ginal effect. These results demonstrated the important role of IL-18 in the resistance and Th1 response of mice to C. neoformans by potentiating the p roduction of IFN-gamma. (C) 2000 Federation of European Microbiological Soc ieties. Published by Elsevier Science B.V. All rights reserved.