{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:43:35Z","timestamp":1790127815941,"version":"4.0.1"},"reference-count":168,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["U19AR076725\u201001"],"award-info":[{"award-number":["U19AR076725\u201001"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic low back pain (cLBP) is a multifactorial condition that can have various contributing factors, including biological, biomechanical, and behavioral. Recent evidence suggests that systemic inflammation may contribute to cLBP, impacting pain sensitivity and individuals' functional status. Circulatory pro\u2010 and anti\u2010inflammatory cytokines are widely used to determine individuals' systemic inflammatory status. The University of Pittsburgh Mechanistic Research Center, part of the National Institutes of Health's (NIH) Helping to End Addiction Long\u2010term Initiative, conducted a prospective, observational study to identify phenotypes in a large cohort of individuals with cLBP. The present work reports the quantification of key circulatory cytokines in this cLBP cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 1007 individuals with cLBP were enrolled. Plasma samples were available from 936 participants, and concentrations of pro\u2010inflammatory (IL\u20106, IFN\u2010\u03b3, TNF, IL\u201015, Leptin) and anti\u2010inflammatory (IL\u20101ra, IL\u201010) cytokines were measured via immunoassays. Pain and functional status were assessed using validated self\u2010reported numeric pain ratings scale and the Oswestry Disability Index. Descriptive statistics of analyzed cytokines were reported across the overall population, stratified by age (&lt;\u200960 and \u2265\u200960\u2009years old) and sex, and by pain levels as mild (0\u20135), moderate (6, 7), and severe (8\u201310), and ODI, categorized as minimal disability (0%\u201320%), moderate (21%\u201340%), and severe disability (&gt;\u200940%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The values of circulating cytokines assessed in this study aligned with those reported in the literature for other painful inflammatory conditions and, in most cases, exceeded those documented for healthy populations. IL\u20106, IL\u20101ra, and Leptin demonstrated higher concentrations with higher pain and disability severity. TNF showed higher concentration in participants with higher disability severity. Concentration levels of IFN\u2010\u03b3, IL\u201015, and IL\u201010 exhibited no differences across pain or ODI categories. Notably, TNF levels were higher in older adults (\u2265\u200960\u2009years), whereas Leptin levels were higher in females than in males.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides a snapshot of key circulating cytokines in a large cLBP cohort, revealing differences in pro\u2010 and anti\u2010inflammatory cytokines across pain and disability for the overall population and in sex and age subgroups. Additional longitudinal and mechanistic studies are required to clarify how cytokines could serve as diagnostic, prognostic, or phenotyping markers, ultimately informing targeted, inflammation\u2010focused therapies that may reshape current treatment approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsp2.70095","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T12:46:47Z","timestamp":1758026807000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Plasma Pro\u2010 and Anti\u2010Inflammatory Cytokines in an Observational Chronic Low Back Pain Cohort"],"prefix":"10.1002","volume":"8","author":[{"given":"Valerio Tonelli","family":"Enrico","sequence":"first","affiliation":[{"name":"Ferguson Laboratory for Spine and Orthopaedic Surgery, Bethel Musculoskeletal Research Center, Department of Orthopaedic Surgery University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0535-0953","authenticated-orcid":false,"given":"William","family":"Anderst","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2099-413X","authenticated-orcid":false,"given":"Kevin M.","family":"Bell","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pittsburgh Swanson School of Engineering  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Paulo","family":"Coelho","sequence":"additional","affiliation":[{"name":"Ferguson Laboratory for Spine and Orthopaedic Surgery, Bethel Musculoskeletal Research Center, Department of Orthopaedic Surgery University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3360-2043","authenticated-orcid":false,"given":"Jessa","family":"Darwin","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Delitto","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy University of Pittsburgh School of Health and Rehabilitation Science  Pittsburgh Pennsylvania USA"},{"name":"Office of the Provost, University of Pittsburgh  Pittsburgh Pennsylvania 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University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Clinical and Translational Science Institute, University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Doctor of Chiropractic Program University of Pittsburgh School of Health and Rehabilitation Science  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Wilcox","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nam V.","family":"Vo","sequence":"additional","affiliation":[{"name":"Ferguson Laboratory for Spine and Orthopaedic Surgery, Bethel Musculoskeletal Research Center, Department of Orthopaedic Surgery University of Pittsburgh School 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