Interleukin-4 weakens host resistance to pulmonary and disseminated cryptococcal infection caused by combined treatment with interferon-γ- inducing cytokines

Kazuyoshi Kawakami, Mahboob Hossain Qureshi, Tiantuo Zhang, Yoshinobu Koguchi, Qifeng Xie, Masashi Kurimoto, Atsushi Saito

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

We examined the role of interleukin (IL)-4 in host resistance against infection with Cryptococcus neoformans. First, we examined the effects of a neutralizing anti-IL-4 monoclonal antibody (mAb) on survival of mice infected intratracheally with this fungal pathogen. We also compared the number of live C. neoformans in lungs and brains of treated and untreated mice. Treatment with anti-IL-4 mAb significantly prolonged survival of infected mice and reduced the lung and brain burdens of C. neoformans, which was associated with increased production of IFN-γ in lungs. In the next experiments, infected mice were treated with two IFN-γ-inducing cytokines, IL-12 and IL-18, known to enhance protection against infection. We then evaluated the effect of such treatment on the number of live microorganisms and concentration of IL-4 in lungs. These two parameters showed a statistically significant relationship, suggesting a negative regulation of host protection by IL-4. Finally, we examined the effects of IL-4 treatment and administration of neutralizing anti-IL-4 mAbs on host protection against C. neoformans and local production of IFN-γ in lungs induced by treatment with IL-12/IL-18. The former treatment suppressed host protection and reduced IFN-γ production, while the latter produced the opposite effects. Our results indicated that IL-4 suppressed the host defense mechanisms against infection with C. neoformans potentiated by IFN-γ-inducing cytokines probably through the suppression of local production of IFN-γ.

Original languageEnglish
Pages (from-to)55-61
Number of pages7
JournalCellular Immunology
Volume197
Issue number1
DOIs
Publication statusPublished - 1999 Oct 10
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Immunology

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