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A cohort of 68 patients was enrolled in the study and periodontal status assessed by the current classification of periodontal diseases. Immune mediators present in saliva, of both patients and healthy controls, were quantified using a Legendplex-13 panel. Clinic parameters were significantly higher in PD patients compared with HC, with a strong significant association with the disease severity (stage) (p &lt; 0.001), but not with progression (grade). The panel of immune mediators evidenced elevated levels of pro-inflammatory cytokines IL-6 and IL-1\u03b2 as disease established (p &lt; 0.01). IL-1\u03b2\/IL-1RA ratio was increased in PD patients, being associated with disease stage. An anti-inflammatory response was spotted by higher IL-10. Lower levels of IL-23 and IP-10 were associated with disease severity. No significant statistical differences were found by grade classification. Moreover, salivary IL-1\u03b2 and IL-6 exhibited significant positive correlations with several clinical measurements (PI, BOP, PPD, CAL), while IP-10 showed a statistical negative correlation with BOP, PPD, and CAL. These insights highlight the complexity of the periodontitis inflammatory network and the potential of cytokines as biomarkers for refined diagnostic and therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms25158401","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T12:38:20Z","timestamp":1722515900000},"page":"8401","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Salivary IL-1\u03b2, IL-6, and IL-10 Are Key Biomarkers of Periodontitis Severity"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0713-2041","authenticated-orcid":false,"given":"Marta","family":"Relvas","sequence":"first","affiliation":[{"name":"University Institute of Health Sciences (IUCS-CESPU), 4585-116 Gandra, Portugal"},{"name":"Oral Pathology and Rehabilitation Research Unit (UNIPRO), University Institute of Health Sciences (IUCS-CESPU), CRL, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7561-5347","authenticated-orcid":false,"given":"Ana","family":"Mendes-Frias","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4710-057 Braga, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"University Institute of Health Sciences (IUCS-CESPU), 4585-116 Gandra, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Toxicologic Pathology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6693-4426","authenticated-orcid":false,"given":"Filomena","family":"Salazar","sequence":"additional","affiliation":[{"name":"University Institute of Health Sciences (IUCS-CESPU), 4585-116 Gandra, Portugal"},{"name":"Oral Pathology and Rehabilitation Research Unit (UNIPRO), University Institute of Health Sciences (IUCS-CESPU), CRL, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7498-8195","authenticated-orcid":false,"given":"Paula","family":"L\u00f3pez-Jarana","sequence":"additional","affiliation":[{"name":"University Institute of Health Sciences (IUCS-CESPU), 4585-116 Gandra, Portugal"},{"name":"Oral Pathology and Rehabilitation Research Unit (UNIPRO), University Institute of Health Sciences (IUCS-CESPU), CRL, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Silvestre","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4710-057 Braga, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2245-5316","authenticated-orcid":false,"given":"Alexandra","family":"Viana da Costa","sequence":"additional","affiliation":[{"name":"University Institute of Health Sciences (IUCS-CESPU), 4585-116 Gandra, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Toxicologic Pathology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/jcpe.12947","article-title":"Manifestations of systemic diseases and conditions that affect the periodontal attachment apparatus: Case definitions and diagnostic considerations","volume":"45","author":"Albandar","year":"2018","journal-title":"J. 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