{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:06:25Z","timestamp":1792062385466,"version":"4.4.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"20","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,10]]},"abstract":"<jats:p>Interleukin 1 receptor antagonist (IL-1ra) is a cytokine whose only known action is competitive inhibition of the binding of interleukin 1 (IL-1) to its receptor. To investigate the physiological roles of endogenously produced IL-1ra, we generated mice that either lack IL-1ra or overproduce it under control of the endogenous promoter. Mice lacking IL-1ra have decreased body mass compared with wild-type controls. They are more susceptible than controls to lethal endotoxemia but are less susceptible to infection with Listeria monocytogenes. Conversely, IL-1ra overproducers are protected from the lethal effects of endotoxin but are more susceptible to listeriosis. Serum levels of IL-1 following an endotoxin challenge are decreased in IL-1ra nulls and increased in IL-1ra overproducers in comparison to controls. These data demonstrate critical roles for endogenously produced IL-1ra in growth, responses to infection and inflammation, and regulation of cytokine expression.<\/jats:p>","DOI":"10.1073\/pnas.93.20.11008","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:16Z","timestamp":1027679656000},"page":"11008-11013","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":259,"title":["Functions of interleukin 1 receptor antagonist in gene knockout and overproducing mice."],"prefix":"10.1073","volume":"93","author":[{"given":"E","family":"Hirsch","sequence":"first","affiliation":[{"name":"Department of Biochemistry, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V M","family":"Irikura","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S M","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Hirsh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1996,10]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.93.20.11008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T15:19:02Z","timestamp":1649863142000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.93.20.11008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,10]]},"references-count":0,"journal-issue":{"issue":"20","published-print":{"date-parts":[[1996,10]]}},"alternative-id":["10.1073\/pnas.93.20.11008"],"URL":"https:\/\/doi.org\/10.1073\/pnas.93.20.11008","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,10]]},"assertion":[{"value":"1996-10-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}