{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:23:06Z","timestamp":1789615386244,"version":"build-2803163510"},"reference-count":181,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"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>To date, the application of oxygen-ozone (O2O3) therapy has significantly increased in the common clinical practice in several pathological conditions. However, beyond the favorable clinical effects, the biochemical effects of O2O3 are still far from being understood. This comprehensive review aimed at investigating the state of the art about the effects of O2O3 therapy on pro-inflammatory cytokines serum levels as a modulator of oxidative stress in patients with musculoskeletal and temporomandibular disorders (TMD). The efficacy of O2O3 therapy could be related to the moderate oxidative stress modulation produced by the interaction of ozone with biological components. More in detail, O2O3 therapy is widely used as an adjuvant therapeutic option in several pathological conditions characterized by chronic inflammatory processes and immune overactivation. In this context, most musculoskeletal and temporomandibular disorders (TMD) share these two pathophysiological processes. Despite the paucity of in vivo studies, this comprehensive review suggests that O2O3 therapy might reduce serum levels of interleukin 6 in patients with TMD, low back pain, knee osteoarthritis and rheumatic diseases with a concrete and measurable interaction with the inflammatory pathway. However, to date, further studies are needed to clarify the effects of this promising therapy on inflammatory mediators and their clinical implications.<\/jats:p>","DOI":"10.3390\/ijms23052528","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T10:00:40Z","timestamp":1645783240000},"page":"2528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":108,"title":["Oxygen-Ozone Therapy for Reducing Pro-Inflammatory Cytokines Serum Levels in Musculoskeletal and Temporomandibular Disorders: A Comprehensive Review"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5541-8346","authenticated-orcid":false,"given":"Alessandro","family":"de Sire","sequence":"first","affiliation":[{"name":"Physical Medicine and Rehabilitation Unit, Department of Medical and Surgical Sciences, University of Catanzaro \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5568-7909","authenticated-orcid":false,"given":"Nicola","family":"Marotta","sequence":"additional","affiliation":[{"name":"Physical Medicine and Rehabilitation Unit, Department of Medical and Surgical Sciences, University of Catanzaro \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1878-4694","authenticated-orcid":false,"given":"Martina","family":"Ferrillo","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Catanzaro \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Agostini","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5345-9902","authenticated-orcid":false,"given":"Cristiano","family":"Sconza","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Research Center, Via Manzoni 56, 20089 Rozzano, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9035-1485","authenticated-orcid":false,"given":"Lorenzo","family":"Lippi","sequence":"additional","affiliation":[{"name":"Physical and Rehabilitative Medicine, Department of Health Sciences, University of Eastern Piedmont \u201cA. Avogadro\u201d, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Respizzi","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Research Center, Via Manzoni 56, 20089 Rozzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9374-0566","authenticated-orcid":false,"given":"Amerigo","family":"Giudice","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Catanzaro \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5141-0681","authenticated-orcid":false,"given":"Marco","family":"Invernizzi","sequence":"additional","affiliation":[{"name":"Physical and Rehabilitative Medicine, Department of Health Sciences, University of Eastern Piedmont \u201cA. Avogadro\u201d, 28100 Novara, Italy"},{"name":"Translational Medicine, Dipartimento Attivit\u00e0 Integrate Ricerca e Innovazione (DAIRI), Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2828-2455","authenticated-orcid":false,"given":"Antonio","family":"Ammendolia","sequence":"additional","affiliation":[{"name":"Physical Medicine and Rehabilitation Unit, Department of Medical and Surgical Sciences, University of Catanzaro \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"ref_1","first-page":"9829176","article-title":"Evolution of the Knowledge of Free Radicals and Other Oxidants","volume":"2020","author":"Venditti","year":"2020","journal-title":"Oxid. Med. Cell. 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