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

研究成果: Article査読

43 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)55-61
ページ数7
ジャーナルCellular Immunology
197
1
DOI
出版ステータスPublished - 1999 10月 10
外部発表はい

ASJC Scopus subject areas

  • 免疫学

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