{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:16:08Z","timestamp":1790356568978,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2001,2,1]],"date-time":"2001-02-01T00:00:00Z","timestamp":980985600000},"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":[[2001,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Underlying viral infections can heighten sensitivity and worsen cytokine-mediated disease following secondary inflammatory challenges. Mechanisms for this are poorly understood. The impact of the innate response to lymphocytic choriomeningitis virus (LCMV) infection on sensitivity to endotoxin (LPS) was investigated. Compared with uninfected mice, infection with LCMV for 2-days-sensitized mice to LPS by \u223c2-fold for lethality and by 2- to 6-fold for serum TNF-\u03b1 levels. Priming for LPS-induced TNF-\u03b1 was also seen with splenic and peritoneal leukocytes isolated from infected mice and challenged with LPS ex vivo. The effect on TNF-\u03b1 production was present in the absence of IFN-\u03b3, its major producers NK and T cells, and the major pathways for its induction through IL-12 and the signal transducer and activator of transcription 4 (STAT4), and therefore was IFN-\u03b3 independent. Early LCMV infection induces high concentrations of the type 1 IFNs, IFN-\u03b1\u03b2. Administration of recombinant IFN-\u03b1 alone heightened the TNF-\u03b1 response to LPS. Innate IFN-\u03b1\u03b2 and IFN-\u03b3 responses to LCMV exist in a delicate balance. To reduce priming for LPS-induced TNF-\u03b1 during LCMV, deficiencies in both the IFN-\u03b1\u03b2 and IFN-\u03b3 receptors or STAT1, a transcription factor downstream to both IFNs, were required. These data demonstrate that early viral infection can enhance sensitivity to bacterial products, and that this sensitization can occur in part as a result of endogenously expressed IFN-\u03b1\u03b2. This work also raises issues about potential complications associated with IFN-\u03b1\u03b2 therapies.<\/jats:p>","DOI":"10.4049\/jimmunol.166.4.2658","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T22:56:08Z","timestamp":1398034568000},"page":"2658-2664","source":"Crossref","is-referenced-by-count":62,"title":["A Role for IFN-\u03b1\u03b2 in Virus Infection-Induced Sensitization to Endotoxin"],"prefix":"10.1093","volume":"166","author":[{"given":"Lesley A","family":"Doughty","sequence":"first","affiliation":[{"name":"Pediatrics, Brown University , Providence, RI 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khuong B","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University , Providence, RI 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan E","family":"Durbin","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pathology, Department of Pediatrics, College of Medicine and Public Health, Ohio State University , Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A","family":"Biron","sequence":"additional","affiliation":[{"name":"Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University , Providence, RI 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2001,2,15]]},"reference":[{"key":"2026020209154126500_R1","first-page":"771","volume-title":"Ann. Intern. Med.","year":"1993"},{"key":"2026020209154126500_R2","first-page":"5049","volume-title":"J. Immunol.","year":"1996"},{"key":"2026020209154126500_R3","first-page":"901","volume-title":"J. Exp. Med.","year":"1995"},{"key":"2026020209154126500_R4","first-page":"5238","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020209154126500_R5","first-page":"456","volume-title":"Sherris Medical Microbiology: An Introduction to Infectious Diseases","year":"1994"},{"key":"2026020209154126500_R6","first-page":"1053","volume-title":"J. Am. Med. Assoc.","year":"1987"},{"key":"2026020209154126500_R7","first-page":"449","volume-title":"J. Infect. Dis.","year":"1968"},{"key":"2026020209154126500_R8","first-page":"1145","volume-title":"Br. Med. J.","year":"1996"},{"key":"2026020209154126500_R9","first-page":"783","volume-title":"Pediatrics","year":"1999"},{"key":"2026020209154126500_R10","first-page":"618","volume-title":"Infect. Immun.","year":"1983"},{"key":"2026020209154126500_R11","first-page":"1189","volume-title":"J. Infect. Dis.","year":"1994"},{"key":"2026020209154126500_R12","first-page":"151","volume-title":"J. Infect. Dis.","year":"1997"},{"key":"2026020209154126500_R13","first-page":"4497","volume-title":"J. Immunol.","year":"1995"},{"key":"2026020209154126500_R14","first-page":"761","volume-title":"Microbiol. Immunol.","year":"1986"},{"key":"2026020209154126500_R15","first-page":"477","volume-title":"Medical Microbiology","year":"1998"},{"key":"2026020209154126500_R16","first-page":"907","volume-title":"J. Exp. Med.","year":"1994"},{"key":"2026020209154126500_R17","first-page":"4244","volume-title":"Infect. Immun.","year":"1994"},{"key":"2026020209154126500_R18","first-page":"672","volume-title":"Eur. J. Immunol.","year":"1995"},{"key":"2026020209154126500_R19","first-page":"1853","volume-title":"J. Exp. Med.","year":"1990"},{"key":"2026020209154126500_R20","first-page":"2920","volume-title":"J. Immunol.","year":"1990"},{"key":"2026020209154126500_R21","first-page":"3972","volume-title":"J. Immunol.","year":"1985"},{"key":"2026020209154126500_R22","first-page":"869","volume-title":"Science","year":"1985"},{"key":"2026020209154126500_R23","first-page":"457","volume-title":"Cell","year":"1993"},{"key":"2026020209154126500_R24","first-page":"657","volume-title":"J. Exp. Med.","year":"1987"},{"key":"2026020209154126500_R25","first-page":"4273","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1987"},{"key":"2026020209154126500_R26","first-page":"1321","volume-title":"J. Clin. Invest.","year":"1988"},{"key":"2026020209154126500_R27","first-page":"665","volume-title":"Nature","year":"1985"},{"key":"2026020209154126500_R28","first-page":"2441","volume-title":"J. Immunol.","year":"1986"},{"key":"2026020209154126500_R29","first-page":"1666","volume-title":"J. Immunol.","year":"1992"},{"key":"2026020209154126500_R30","first-page":"2325","volume-title":"J. Immunol.","year":"1989"},{"key":"2026020209154126500_R31","first-page":"1536","volume-title":"J. Immunol.","year":"1988"},{"key":"2026020209154126500_R32"},{"key":"2026020209154126500_R33","first-page":"383","volume-title":"Semin. Immunol.","year":"1998"},{"key":"2026020209154126500_R34","first-page":"634","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1997"},{"key":"2026020209154126500_R35","first-page":"70","volume-title":"Nat. Immunol.","year":"2000"},{"key":"2026020209154126500_R36","first-page":"2489","volume-title":"Cancer Res.","year":"1998"},{"key":"2026020209154126500_R37","first-page":"2444","volume-title":"J Clin. Oncol.","year":"2000"},{"key":"2026020209154126500_R38","first-page":"99","volume-title":"Eur. Cytokine Network","year":"2000"},{"key":"2026020209154126500_R39","first-page":"495","volume-title":"Int. J. Lepr. Other Mycobact. Dis.","year":"1997"},{"key":"2026020209154126500_R40","first-page":"9402","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1994"},{"key":"2026020209154126500_R41","first-page":"869","volume-title":"Cell","year":"1992"},{"key":"2026020209154126500_R42","first-page":"5007","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020209154126500_R43","first-page":"1045","volume-title":"J. Exp. Med.","year":"1995"},{"key":"2026020209154126500_R44","first-page":"171","volume-title":"Nature","year":"1996"},{"key":"2026020209154126500_R45","first-page":"7417","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020209154126500_R46","first-page":"206","volume-title":"Infect. Immun.","year":"1999"},{"key":"2026020209154126500_R47","first-page":"3097","volume-title":"Eur. J. Immunol.","year":"1993"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/166\/4\/2658\/62536703\/2658.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/166\/4\/2658\/62536703\/2658.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:21:37Z","timestamp":1770042097000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/166\/4\/2658\/8025907"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,2]]},"references-count":47,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2001,2,15]]},"published-print":{"date-parts":[[2001,2,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.166.4.2658","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2001,2]]},"published":{"date-parts":[[2001,2]]}}}