{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T11:03:14Z","timestamp":1793876594903,"version":"4.7.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2000,6,1]],"date-time":"2000-06-01T00:00:00Z","timestamp":959817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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-\u03b3, TNF-\u03b1, 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.<\/jats:p>","DOI":"10.4049\/jimmunol.164.12.6406","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:59:29Z","timestamp":1398031169000},"page":"6406-6416","source":"Crossref","is-referenced-by-count":362,"title":["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"],"prefix":"10.1093","volume":"164","author":[{"given":"Karl F","family":"Hoffmann","sequence":"first","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen W","family":"Cheever","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute , Rockville, MD 20852"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A","family":"Wynn","sequence":"additional","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,6,15]]},"reference":[{"key":"2026020214035507000_R1","first-page":"798","volume-title":"J. 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