{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:28:34Z","timestamp":1791412114391,"version":"4.3.3"},"reference-count":33,"publisher":"Rockefeller University Press","issue":"9","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,8,31]]},"abstract":"<jats:p>Tumor necrosis factor (TNF) is reputed to have very powerful antitumor effects, but it is also a strong proinflammatory cytokine. Injection of TNF in humans and mice leads to a systemic inflammatory response syndrome with major effects on liver and bowels. TNF is also a central mediator in several inflammatory diseases. We report that type I interferons (IFNs) are essential mediators of the lethal response to TNF. Mice deficient in the IFN-\u03b1 receptor 1 (IFNAR-1) or in IFN-\u03b2 are remarkably resistant to TNF-induced hypothermia and death. After TNF injection, IFNAR-1\u2212\/\u2212 mice produced less IL-6, had less bowel damage, and had less apoptosis of enterocytes and hepatocytes compared with wild-type (WT) mice. Extensive gene expression analysis in livers of WT and IFNAR-1\u2212\/\u2212 mice revealed a large deficiency in the response to TNF in the knockout mice, especially of IFN-stimulated response element\u2013dependent genes, many of which encode chemokines. In livers of IFNAR-1\u2212\/\u2212 mice, fewer infiltrating white blood cells (WBCs) were detected by immunohistochemistry. Deficiency of type I IFN signaling provided sufficient protection for potentially safer therapeutic use of TNF in tumor-bearing mice. Our data illustrate that type I IFNs act as essential mediators in TNF-induced lethal inflammatory shock, possibly by enhancing cell death and inducing chemokines and WBC infiltration in tissues.<\/jats:p>","DOI":"10.1084\/jem.20090213","type":"journal-article","created":{"date-parts":[[2009,8,18]],"date-time":"2009-08-18T01:52:05Z","timestamp":1250560325000},"page":"1873-1882","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":77,"title":["Type I interferon drives tumor necrosis factor\u2013induced lethal shock"],"prefix":"10.1084","volume":"206","author":[{"given":"Liesbeth","family":"Huys","sequence":"first","affiliation":[{"name":"Department for Molecular Biomedical Research, VIB, Ghent B9052, Belgium 1"},{"name":"Department of Biomedical Molecular Biology, Ghent University, Ghent B9052, Belgium 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Van Hauwermeiren","sequence":"additional","affiliation":[{"name":"Department for Molecular Biomedical Research, VIB, Ghent B9052, Belgium 1"},{"name":"Department of Biomedical Molecular Biology, Ghent University, Ghent B9052, Belgium 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lien","family":"Dejager","sequence":"additional","affiliation":[{"name":"Department for Molecular Biomedical Research, VIB, Ghent B9052, Belgium 1"},{"name":"Department of Biomedical Molecular Biology, Ghent University, Ghent B9052, Belgium 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline","family":"Dejonckheere","sequence":"additional","affiliation":[{"name":"Department for Molecular Biomedical Research, VIB, Ghent B9052, Belgium 1"},{"name":"Department of Biomedical Molecular Biology, Ghent University, Ghent B9052, Belgium 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Lienenklaus","sequence":"additional","affiliation":[{"name":"Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig D-38124, Germany 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegfried","family":"Weiss","sequence":"additional","affiliation":[{"name":"Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig D-38124, Germany 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Leclercq","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, Ghent B-9000, Belgium 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Libert","sequence":"additional","affiliation":[{"name":"Department for Molecular Biomedical Research, VIB, Ghent B9052, Belgium 1"},{"name":"Department of Biomedical Molecular Biology, Ghent University, Ghent B9052, Belgium 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2009,8,17]]},"reference":[{"key":"2023072917342667900_bib1","first-page":"93","article-title":"Tumor necrosis factors: developments during the last decade","volume":"7","author":"Aggarwal","year":"1996","journal-title":"Eur. 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