{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T20:09:36Z","timestamp":1775160576095,"version":"3.50.1"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"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":[[2015,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Both IL-1\u03b1 and IL-1\u03b2 are highly inflammatory cytokines mediating a wide spectrum of diseases. A recombinant form of the naturally occurring IL-1R antagonist (IL-1Ra), which blocks IL-1R1, is broadly used to treat autoimmune and autoinflammatory diseases; however, blocking IL-1 increases the risk of infection. In this study, we describe the development of a novel form of recombinant IL-1Ra, termed chimeric IL-1Ra. This molecule is a fusion of the N-terminal peptide of IL-1\u03b2 and IL-1Ra, resulting in inactive IL-1Ra. Because the IL-1\u03b2 N-terminal peptide contains several protease sites clustered around the caspase-1 site, local proteases at sites of inflammation can cleave chimeric IL-1Ra and turn IL-1Ra active. We demonstrate that chimeric IL-1Ra reduces IL-1\u2013mediated inflammation in vitro and in vivo. This unique approach limits IL-1 receptor blockade to sites of inflammation, while sparing a multitude of desired IL-1\u2013related activities, including host defense against infections and IL-1\u2013mediated repair.<\/jats:p>","DOI":"10.4049\/jimmunol.1501168","type":"journal-article","created":{"date-parts":[[2015,7,9]],"date-time":"2015-07-09T01:56:04Z","timestamp":1436406964000},"page":"1705-1712","source":"Crossref","is-referenced-by-count":10,"title":["IL-1 Receptor Antagonist Chimeric Protein: Context-Specific and Inflammation-Restricted Activation"],"prefix":"10.1093","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3265-946X","authenticated-orcid":false,"given":"Peleg","family":"Rider","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva 84105 ,","place":["Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaron","family":"Carmi","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Stanford University , Palo Alto, CA 95305"},{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics and The Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva 84105 ,","place":["Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rami","family":"Yossef","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics and The Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva 84105 ,","place":["Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ofer","family":"Guttman","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva 84105 ,","place":["Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hadar","family":"Eini","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva 84105 ,","place":["Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Azam","sequence":"additional","affiliation":[{"name":"University of Colorado at Denver , Aurora, CO 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles A","family":"Dinarello","sequence":"additional","affiliation":[{"name":"University of Colorado at Denver , Aurora, CO 80045"},{"name":"Radboud University Medical Centre , Nijmegen 6500 ,","place":["the Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eli C","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva 84105 ,","place":["Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,8,15]]},"reference":[{"key":"2025030704045411000_r1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.smim.2013.10.001","article-title":"Overview of the interleukin-1 family of ligands and receptors","volume":"25","author":"Dinarello","year":"2013","journal-title":"Semin. 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