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

First Author  Kawakami K Year  1999
Journal  Cell Immunol Volume  197
Issue  1 Pages  55-61
PubMed ID  10555996 Mgi Jnum  J:58585
Mgi Id  MGI:1349247 Doi  10.1006/cimm.1999.1557
Citation  Kawakami K, et al. (1999) Interleukin-4 weakens host resistance to pulmonary and disseminated cryptococcal infection caused by combined treatment with interferon-gamma-inducing cytokines. Cell Immunol 197(1):55-61
abstractText  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-gamma in lungs. In the next experiments, infected mice were treated with two IFN-gamma-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-gamma in lungs induced by treatment with IL-12/IL-18. The former treatment suppressed host protection and reduced IFN-gamma 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-gamma-inducing cytokines probably through the suppression of local production of IFN-gamma. Copyright 1999 Academic Press.
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