{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:43:07Z","timestamp":1790808187146,"version":"4.1.0"},"reference-count":64,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T00:00:00Z","timestamp":1552521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Interleukin-1 (IL-1)\u03b2 and IL-1 receptor antagonist (IL-1Ra) have been proposed as important mediators during chronic liver diseases. We aimed to determine whether the modulation of IL-1\u03b2 signaling with IL-1Ra impacts on liver fibrosis. Methods: We assessed the effects of IL-1\u03b2 on human hepatic stellate cells (HSC) and in mouse models of liver fibrosis induced by bile duct ligation (BDL) or carbon tetrachloride treatment (CCl-4). Results: Human HSCs treated with IL-1\u03b2 had increased IL-1\u03b2, IL-1Ra, and MMP-9 expressions in vitro. HSCs treated with IL-1\u03b2 had reduced \u03b1-smooth muscle actin expression. These effects were all prevented by IL-1Ra treatment. In the BDL model, liver fibrosis and Kuppfer cell numbers were increased in IL-1Ra KO mice compared to wild type mice and wild type mice treated with IL-1Ra. In contrast, after CCl-4 treatment, fibrosis, HSC and Kupffer cell numbers were decreased in IL-1Ra KO mice compared to the other groups. IL-1Ra treatment provided a modest protective effect in the BDL model and was pro-fibrotic in the CCl-4 model. Conclusions: We demonstrated bivalent effects of IL-1Ra during liver fibrosis in mice. IL-1Ra was detrimental in the CCl-4 model, whereas it was protective in the BDL model. Altogether these data suggest that blocking IL-1-mediated inflammation may be beneficial only in selective liver fibrotic disease.<\/jats:p>","DOI":"10.3390\/ijms20061295","type":"journal-article","created":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T04:12:09Z","timestamp":1552623129000},"page":"1295","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Interleukin-1 Receptor Antagonist Modulates Liver Inflammation and Fibrosis in Mice in a Model-Dependent Manner"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9050-0436","authenticated-orcid":false,"given":"Raphael P. H.","family":"Meier","sequence":"first","affiliation":[{"name":"Visceral and Transplant Surgery, Department of Surgery, Geneva University Hospitals and Medical School, 1211 Geneva, Switzerland"},{"name":"Transplant Surgery, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Meyer","sequence":"additional","affiliation":[{"name":"Visceral and Transplant Surgery, Department of Surgery, Geneva University Hospitals and Medical School, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Montanari","sequence":"additional","affiliation":[{"name":"Visceral and Transplant Surgery, Department of Surgery, Geneva University Hospitals and Medical School, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5921-6389","authenticated-orcid":false,"given":"Stephanie","family":"Lacotte","sequence":"additional","affiliation":[{"name":"Visceral and Transplant Surgery, Department of Surgery, Geneva University Hospitals and Medical School, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9039-6579","authenticated-orcid":false,"given":"Alexandre","family":"Balaphas","sequence":"additional","affiliation":[{"name":"Visceral and Transplant Surgery, Department of Surgery, Geneva University Hospitals and Medical School, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick D.","family":"Muller","sequence":"additional","affiliation":[{"name":"Transplant Surgery, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Cl\u00e9ment","sequence":"additional","affiliation":[{"name":"Division of Clinical Pathology, Geneva University Hospitals and Medical School, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Negro","sequence":"additional","affiliation":[{"name":"Division of Clinical Pathology, Geneva University Hospitals and Medical School, 1211 Geneva, Switzerland"},{"name":"Division of Gastroenterology and Hepatology, Geneva University Hospitals and Medical School, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Toso","sequence":"additional","affiliation":[{"name":"Visceral and Transplant Surgery, Department of Surgery, Geneva University Hospitals and Medical School, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Morel","sequence":"additional","affiliation":[{"name":"Visceral and Transplant Surgery, Department of Surgery, Geneva University Hospitals and Medical School, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo H.","family":"Buhler","sequence":"additional","affiliation":[{"name":"Visceral and Transplant Surgery, Department of Surgery, Geneva University Hospitals and Medical School, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1056\/NEJMe0811014","article-title":"Interleukin-1beta and the autoinflammatory diseases","volume":"360","author":"Dinarello","year":"2009","journal-title":"New Engl. 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