{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:43:31Z","timestamp":1791585811071,"version":"4.3.4"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001625","name":"foundation to eradicate duchenne","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001625","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Muscle inflammation is one of the hallmarks of Duchenne muscular dystrophy (DMD). Dystrophin-deficient skeletal muscle cells produce higher levels of pro-inflammatory cytokines such as interleukin 1\u03b2 (IL-1\u03b2) in response to toll-like receptor stimulation compared to normal muscle skeletal cells. IL- 1\u03b2 induces the human skeletal muscle secretion of the myokine Interleukin-6 (IL-6). Here, we evaluated the effect of a human IgG1\u03ba monoclonal antibody (canakinumab (Ilaris\u00ae)) that specifically blocks the IL-1\u03b2 effect on IL-6 secretion by human skeletal muscle cells. Canakinumab is an excellent candidate for therapeutic repositioning to treat DMD because it is an FDA-approved drug to treat periodic fever syndromes and systemic juvenile idiopathic arthritis. Unlike previous generations of IL-1 inhibitors, canakinumab is highly specific for the IL-1\u03b2 ligand, has a longer half-life, and does not interfere with other IL-1-activated inflammatory pathways. Following cell culture optimization and viability assays to assess toxicity, skeletal muscle cells were stimulated with IL-1\u03b2 (10\u2009ng\/mL) for 48 hours in the presence of nine concentrations of canakinumab ranging from 0.001\u2009nM to 1000\u2009nM, and IL-6 production was measured with an enzyme-linked immunosorbent assay. Pre-incubation of myoblasts with canakinumab before IL-1\u03b2-stimulation, significantly reduced IL-6 production at concentrations of 1, 10, 100, 250, and 1000\u2009nM relative to controls, yielding an IC\n                    <jats:sub>50<\/jats:sub>\n                    of 0.264\u2009nM. On the other hand, co-incubation of canakinumab with IL-1\u03b2 before addition to myoblasts resulted in a significant inhibition with the IC\n                    <jats:sub>50<\/jats:sub>\n                    reducing to 0.126\u2009nM, less than half of the previous method. Canakinumab also did not affect myotube viability at 10\u2009nM and was also able to significantly reduce the production of IL-6, when the cells were stimulated with IL-1\u03b2 (10\u2009ng\/ml). Taken together, our results show that canakinumab is a potent inhibitor of IL-1\u03b2 signaling in muscle cells. These results align with previously published pre-clinical work with other IL-1 inhibitors in the mdx mouse model and support further investigation into the clinical utility of repositioning canakinumab to treat DMD.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0316110","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T13:23:28Z","timestamp":1741267408000},"page":"e0316110","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["The effect of IL-1\u03b2 inhibitor canakinumab (Ilaris\u00ae) on IL-6 production in human skeletal muscle cells"],"prefix":"10.1371","volume":"20","author":[{"given":"Anna","family":"Cordeiro-Santanach","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiorella","family":"Morales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria del Carmen","family":"Parquet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kitipong","family":"Uaesoontrachoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Rowsell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Warford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Elustondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric P.","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanneboyina","family":"Nagaraju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"issue":"1","key":"pone.0316110.ref001","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S1474-4422(09)70271-6","article-title":"Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management","volume":"9","author":"K Bushby","year":"2010","journal-title":"Lancet Neurol"},{"issue":"299","key":"pone.0316110.ref002","doi-asserted-by":"crossref","first-page":"299rv4","DOI":"10.1126\/scitranslmed.aaa7322","article-title":"Immune-mediated pathology in Duchenne muscular dystrophy","volume":"7","author":"AS Rosenberg","year":"2015","journal-title":"Sci Transl 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Genetics"},{"key":"pone.0316110.ref007","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.semcdb.2016.09.013","article-title":"Fibrosis development in early-onset muscular dystrophies: Mechanisms and translational implications","volume":"64","author":"AL Serrano","year":"2017","journal-title":"Semin Cell Dev Biol"},{"issue":"2","key":"pone.0316110.ref008","doi-asserted-by":"crossref","first-page":"R345-53","DOI":"10.1152\/ajpregu.00454.2004","article-title":"Inflammatory processes in muscle injury and repair","volume":"288","author":"JG Tidball","year":"2005","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"issue":"1","key":"pone.0316110.ref009","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1083\/jcb.201402079","article-title":"Asynchronous remodeling is a driver of failed regeneration in Duchenne muscular dystrophy","volume":"207","author":"S Dadgar","year":"2014","journal-title":"J Cell Biol"},{"issue":"9","key":"pone.0316110.ref010","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/S1474-4422(22)00125-9","article-title":"Emerging therapies for Duchenne muscular dystrophy","volume":"21","author":"T Markati","year":"2022","journal-title":"Lancet Neurol"},{"issue":"1","key":"pone.0316110.ref011","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s13023-021-01758-9","article-title":"Standard of care versus new-wave corticosteroids in the treatment of Duchenne muscular dystrophy: Can we do better?","volume":"16","author":"S Kourakis","year":"2021","journal-title":"Orphanet J Rare Dis"},{"issue":"6","key":"pone.0316110.ref012","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.3233\/JND-230161","article-title":"Considering the promise of vamorolone for treating Duchenne muscular dystrophy","volume":"10","author":"M Grounds","year":"2023","journal-title":"Journal of Neuromuscular 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results from the 5-year long-term extension of the phase III pivotal trials","volume":"77","author":"N Ruperto","year":"2018","journal-title":"Ann Rheum Dis"},{"issue":"4","key":"pone.0316110.ref031","first-page":"668","article-title":"Efficacy and safety of canakinumab in patients with Still\u2019s disease: exposure-response analysis of pooled systemic juvenile idiopathic arthritis data by age groups","volume":"36","author":"E Feist","year":"2018","journal-title":"Clin Exp Rheumatol"},{"issue":"8","key":"pone.0316110.ref032","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.3390\/jcm8081109","article-title":"Inflammation as a therapeutic target in atherosclerosis","volume":"8","author":"M Nguyen","year":"2019","journal-title":"J Clin Med"},{"issue":"5","key":"pone.0316110.ref033","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1111\/bjd.14037","article-title":"Canakinumab in adults with steroid-refractory pyoderma gangrenosum","volume":"173","author":"AGA Kolios","year":"2015","journal-title":"Br J Dermatol"},{"issue":"2","key":"pone.0316110.ref034","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/bph.13798","article-title":"Drug repurposing from the perspective of pharmaceutical companies","volume":"175","author":"Y Cha","year":"2018","journal-title":"Br J Pharmacol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0316110","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T13:23:43Z","timestamp":1741267423000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0316110"}},"subtitle":[],"editor":[{"given":"Charles Neil","family":"Pagel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,3,6]]},"references-count":34,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0316110","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,6]]}}}