{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:20:52Z","timestamp":1791415252095,"version":"4.3.3"},"reference-count":62,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council Career Development Award Fellowship","award":["MR\/X007243\/1"],"award-info":[{"award-number":["MR\/X007243\/1"]}]},{"DOI":"10.13039\/501100013629","name":"NIHR Surgical Reconstruction and Microbiology Research Centre","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013629","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100011696","name":"Scar Free Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100011696","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Major trauma induces innate immune suppression, yet the underlying mechanisms are poorly understood. Resistin is an immunosuppressive molecule that is systemically elevated post-injury. However, its role in trauma-induced immune dysfunction and clinical outcomes is poorly defined. Here, we acquired blood samples from 147 adult trauma patients (\u22641, 4\u201312, 48\u201372 h post-injury) and 95 burns patients (days 1, 3, 7, 14, 28 post-burn). We measured plasma resistin concentrations, studied resistin gene expression in peripheral blood mononuclear cells (PBMCs) and neutrophils, and measured resistin production by lipopolysaccharide (LPS)-challenged whole blood leukocytes. To identify potential novel triggers of resistin secretion by immune cells, we examined the effect that stimulation with mitochondrial-derived damage-associated molecular patterns (mtDAMPs) had on resistin production by neutrophils isolated from healthy donors. We also treated neutrophils, from healthy donors, and THP-1 cells with resistin prior to stimulation with Phorbol 12-myristate-13-acetate (PMA) or LPS to study its effects on reactive oxygen species (ROS) and cytokine production, respectively. Injured patients presented with significantly elevated circulating resistin concentrations and increased resistin gene expression in PBMCs and neutrophils. LPS and mtDAMP stimulation promoted resistin secretion by whole blood leukocytes and neutrophils. Plasma resistin concentrations were negatively associated with PMA-induced ROS generation by neutrophils, and LPS-induced cytokine production by monocytes. Resistin-treated THP-1 cells and neutrophils exhibited impaired functional responses upon secondary stimulation with LPS or PMA, respectively. Trauma patients who developed multiple organ dysfunction syndrome (MODS) presented with significantly elevated resistin concentrations, which at 48\u201372 h post-injury showed good performance as a predictor of post-traumatic MODS (AUROC, 0.796). Hyperresistinemia is an immediate and persistent feature of the inflammatory response to injury that may contribute to the development of innate immune dysfunction.<\/jats:p>","DOI":"10.3390\/biom16030443","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:13:14Z","timestamp":1773659594000},"page":"443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Major Traumatic and Severe Thermal Injuries Lead to Immediate and Persistent Elevations in Circulating Concentrations of Resistin That Are Associated with Poor Clinical Outcomes and Impaired Innate Immune Responses"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8573-0247","authenticated-orcid":false,"given":"Emily","family":"Horner","sequence":"first","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsty C.","family":"McGee","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, Birmingham B15 2TH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1117-0801","authenticated-orcid":false,"given":"Sebastian","family":"Tullie","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2GW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2243-2325","authenticated-orcid":false,"given":"David N.","family":"Naumann","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2GW, UK"},{"name":"Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine, Queen Elizabeth Hospital Birmingham, Birmingham B15 2GW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2735-7010","authenticated-orcid":false,"given":"Animesh","family":"Acharjee","sequence":"additional","affiliation":[{"name":"Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Lissillour","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Asiri","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice M. S.","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda V.","family":"Sardeli","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4610-8909","authenticated-orcid":false,"given":"Paul","family":"Harrison","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"The Scar Free Foundation Centre for Conflict Wound Research, Queen Elizabeth Hospital Birmingham, Birmingham B15 2GW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3211-9933","authenticated-orcid":false,"given":"Antonio","family":"Belli","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2GW, UK"},{"name":"National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham, Birmingham B15 2GW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0836-5138","authenticated-orcid":false,"given":"Naiem S.","family":"Moiemen","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2GW, UK"},{"name":"The Scar Free Foundation Centre for Conflict Wound Research, Queen Elizabeth Hospital Birmingham, Birmingham B15 2GW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet M.","family":"Lord","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"The Scar Free Foundation Centre for Conflict Wound Research, Queen Elizabeth Hospital Birmingham, Birmingham B15 2GW, UK"},{"name":"National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham, Birmingham B15 2GW, UK"},{"name":"MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4280-4889","authenticated-orcid":false,"given":"Jon","family":"Hazeldine","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, Birmingham B15 2TH, UK"},{"name":"National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham, Birmingham B15 2GW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nicholson, T., Belli, A., Lord, J.M., and Hazeldine, J. 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