TY - JOUR
T1 - Involvement of endogenously synthesized interleukin (IL)-18 in the protective effects of IL-12 against pulmonary infection with Cryptococcus neoformans in mice
AU - Kawakami, Kazuyoshi
AU - Qureshi, Mahboob Hossain
AU - Zhang, Tiantuo
AU - Koguchi, Yoshinobu
AU - Yara, Satomi
AU - Takeda, Kiyoshi
AU - Akira, Shizuo
AU - Kurimoto, Masashi
AU - Saito, Atsushi
N1 - Funding Information:
This work was supported in part by the Grant-in-Aid for Scientific Research (C) (09670292) from the Ministry of Education, Science, Sport and Culture, by grants from the Ministry of Health and Welfare, Japan, and the Japan Health Science Foundation. The authors thank Dr. F.G. Issa (Word-Medex, Sydney, Australia) for editing the manuscript.
PY - 2000/3
Y1 - 2000/3
N2 - 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. Copyright (C) 2000 Elsevier Science B.V.
AB - 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. Copyright (C) 2000 Elsevier Science B.V.
KW - Cryptococcus neoformans
KW - Host defense
KW - Interferon-γ
KW - Interleukin-12
KW - Interleukin-18
KW - Lung
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U2 - 10.1016/S0928-8244(99)00181-9
DO - 10.1016/S0928-8244(99)00181-9
M3 - Article
C2 - 10683463
AN - SCOPUS:0033953315
VL - 27
SP - 191
EP - 200
JO - Pathogens and Disease
JF - Pathogens and Disease
SN - 2049-632X
IS - 3
ER -