Send to

Choose Destination
See comment in PubMed Commons below
J Immunol. 2000 Jun 15;164(12):6406-16.

IL-10 and the dangers of immune polarization: excessive type 1 and type 2 cytokine responses induce distinct forms of lethal immunopathology in murine schistosomiasis.

Author information

Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.


To dissect the controversial roles of type 1 and type 2 cytokines to the pathogenesis of schistosomiasis, we generated IL-10/IL-4- and IL-10/IL-12-deficient mice that develop highly polarized type 1 and type 2 cytokine responses, respectively. Interestingly, the Th1-polarized IL-10/IL-4-deficient mice rapidly lost weight at the onset of egg-laying and displayed 100% mortality by wk 9 postinfection. This acute mortality was linked to overexpression of the proinflammatory mediators IFN-gamma, TNF-alpha, and inducible NO and the formation of nonfibrotic granulomas. Elevated serum aspartate transaminase levels confirmed that mortality was in part attributable to acute hepatotoxicity. In contrast, the Th2-polarized IL-10/IL-12-deficient mice developed a progressive wasting disease that correlated with increased hepatic fibrosis, formation of large eosinophil-rich granulomas, a 10-fold increase in IL-4 and IL-13, and significant mortality during the chronic stages of infection. Surprisingly, IL-10-deficient mice displayed pathological features that were characteristic of both extremes, while wild-type mice developed relatively successful long term chronic infections. These data demonstrate that IL-10 significantly suppresses type 1 and type 2 cytokine development in IL-4- and IL-12-deficient mice, respectively, thereby impeding the development of severe egg-induced pathology in the single cytokine-deficient animals. Together, these findings reveal the central regulatory role of IL-10 in the pathogenesis of schistosomiasis and illustrate that excessive type 1 and type 2 cytokine responses trigger distinct, but equally detrimental, forms of pathology following infection.

[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center