Combined effects of IL-12 and IL-18 on the clinical course and local cytokine production in murine pulmonary infection with Cryptococcus neoformans

Mahboob Hossain Qureshi, Tiantuo Zhang, Yoshinobu Koguchi, Kazutoshi Nakashima, Haruki Okamura, Masashi Kurimoto, Kazuyoshi Kawakami

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

We reported recently that interleukin (IL)-12 and IL-18 synergistically increased the fungicidal activity of mouse peritoneal exudate cells against Cryptococcus neoformans by inducing the production of interferon (IFN)-γ by natural killer (NK) cells. To confirm these findings in vivo, we examined the effect of combined treatment using these two cytokines on the course of experimentally induced pulmonary and disseminated cryptococcosis in mice. IL-12 and IL-18 were used at subtherapeutic doses (0.005 and 2 μg/mouse/day, respectively). A single administration of either cytokine was not effective in protecting mice against the infection, while combined treatment significantly prolonged survival time of infected mice and reduced the lung and brain loads of organisms. These protective effects were associated with elevated IFN-γ and reduced IL-4 levels in bronchoalveolar lavage fluid. Finally, depletion of NK and γδ T cells, but not of CD4+ T cells, by administration of specific antibodies, significantly reduced the production of IFN-γ in lungs by IL-12/IL-18 treatment during the 7 days of infection. Our results demonstrated that IL-12 and IL-18 protected mice against cryptococcal infection in a synergistic manner by enhancing the local production of IFN-γ by NK and γδ T cells in the early phase of infection and by suppressing the production of IL-4 in lungs.

Original languageEnglish
Pages (from-to)643-649
Number of pages7
JournalEuropean Journal of Immunology
Volume29
Issue number2
DOIs
Publication statusPublished - 1999 Feb 19
Externally publishedYes

Keywords

  • Cryptococcus neoformans
  • IFN-γ
  • IL-12
  • IL-18
  • IL-4

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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