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Reid Charitable Trusts","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008322","name":"CSL Behring","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1154235"],"award-info":[{"award-number":["1154235"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1113577"],"award-info":[{"award-number":["1113577"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp;amp; Trans Imm"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Rheumatoid arthritis (RA), an inflammatory joint disorder, independently increases the risk of cardiovascular disease (CVD). IL\u20101\u03b2 contributes to both RA and CVD. We hypothesised that inhibiting IL\u20101 signalling with the IL\u20101R antagonist, anakinra, would dampen inflammation and promote resolution of atherosclerosis in arthritic mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Low\u2010density lipoprotein receptor (Ldlr)\u2010deficient mice were fed a Western\u2010type diet for 14\u00a0weeks to develop atherosclerotic plaques. Mice were then switched to a chow diet, promoting lesion regression, and randomised to a control group or into groups where arthritis was induced by passive transfer of K\/BxN arthritogenic serum. The arthritic mice were further randomised to vehicle or anakinra.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Arthritis impaired atherosclerotic lesion regression when cholesterol was lowered. This was associated with a higher burden of plaque macrophages, likely due to monocytosis, driven by myelopoiesis in the bone marrow and spleen. Interestingly, delayed intervention with anakinra had no effect on arthritis in these mice. However, a significant improvement in atherosclerotic plaque remodelling to a more stable phenotype was observed. This was associated with fewer circulating monocytes, caused by a reduction in splenic extramedullary myelopoiesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We show that inhibiting IL\u20101 signalling in arthritic mice with pre\u2010existing atherosclerosis promotes lesion remodelling to a more stable phenotype, that is less likely to rupture and cause ischemic events such as myocardial infarction. This suggests that IL\u20101R antagonism may suppress CVD complications in patients with RA. Furthermore, inhibiting IL\u20101\u03b2 signalling in other patients with inflammatory diseases that also predispose to CVD may also benefit from anti\u2010IL\u20101 therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1206","type":"journal-article","created":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T00:42:57Z","timestamp":1604968977000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Inhibition of interleukin\u20101\u03b2 signalling promotes atherosclerotic lesion remodelling in mice with inflammatory arthritis"],"prefix":"10.1002","volume":"9","author":[{"given":"Dragana","family":"Dragoljevic","sequence":"first","affiliation":[{"name":"Division of Immunometabolism Baker Heart and Diabetes Institute Melbourne VIC Australia"},{"name":"Department of Immunology Monash University Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man Kit Sam","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Immunometabolism Baker Heart and Diabetes Institute Melbourne VIC Australia"},{"name":"Department of Immunology Monash University Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Louis","sequence":"additional","affiliation":[{"name":"Inflammation Division Walter and Eliza Hall Institute of Medical Research Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waled","family":"Shihata","sequence":"additional","affiliation":[{"name":"Division of Immunometabolism Baker Heart and Diabetes Institute Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Kraakman","sequence":"additional","affiliation":[{"name":"Division of Immunometabolism Baker Heart and Diabetes Institute Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacinta","family":"Hansen","sequence":"additional","affiliation":[{"name":"Inflammation Division Walter and Eliza Hall Institute of Medical Research Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4763-576X","authenticated-orcid":false,"given":"Seth L","family":"Masters","sequence":"additional","affiliation":[{"name":"Inflammation Division Walter and Eliza Hall Institute of Medical Research Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz Y","family":"Hanaoka","sequence":"additional","affiliation":[{"name":"Department of Surgery Ohio State University Wexner Medical Center Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0294-641X","authenticated-orcid":false,"given":"Prabhakara R","family":"Nagareddy","sequence":"additional","affiliation":[{"name":"Department of Surgery Ohio State University Wexner Medical Center Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme I","family":"Lancaster","sequence":"additional","affiliation":[{"name":"Division of Immunometabolism Baker Heart and Diabetes Institute Melbourne VIC Australia"},{"name":"Department of Immunology Monash University Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian P","family":"Wicks","sequence":"additional","affiliation":[{"name":"Inflammation Division Walter and Eliza Hall Institute of Medical Research Melbourne VIC Australia"},{"name":"Rheumatology Unit Royal Melbourne Hospital Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J","family":"Murphy","sequence":"additional","affiliation":[{"name":"Division of Immunometabolism Baker Heart and Diabetes Institute Melbourne VIC 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