{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T08:26:01Z","timestamp":1765182361664,"version":"3.46.0"},"reference-count":39,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T00:00:00Z","timestamp":1764979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Research Grant of the Hungarian Association of Rheumatology 2024","award":["MRE\/KP\/I\/3"],"award-info":[{"award-number":["MRE\/KP\/I\/3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Kynurenic acid (KYNA) has recognized anti-inflammatory and immunosuppressive properties. Previous studies demonstrated that KYNA reduces TNF-\u03b1, S100A12, S100A8\/9, and \u03b1-defensin production while increasing tumor necrosis factor-stimulated gene-6 protein (TSG-6) levels in rheumatoid arthritis. This study evaluated a synthetic KYNA analog\u2019s effects on TNF-\u03b1, S100A8\/9, S100A12, \u03b1-defensin, and interleukin-17 (IL-17) production and TSG-6 expression in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Peripheral blood mononuclear cells from 54 AS and 38 PsA patients and 11 healthy controls were stimulated with heat-inactivated Staphylococcus aureus (SA1). Parallel cultures were pretreated with the KYNA analog. Cytokine and alarmin concentrations were measured by ELISA. SA1 stimulation increased TNF-\u03b1, TSG-6, calprotectin, and \u03b1-defensin production, with minimal effects on S100A12 and none on IL-17. The KYNA analog significantly reduced SA1-induced TNF-\u03b1, calprotectin, and \u03b1-defensin levels and enhanced TSG-6 production, without affecting S100A12 or IL-17. Notably, the TNF-\u03b1 inhibitory and TSG-6 stimulatory effects were inversely correlated. Conclusion: KYNA analogs may exert anti-inflammatory effects via TSG-6 upregulation, contributing to the suppression of key cytokines. These findings support further exploration of KYNA derivatives as therapeutic options in immune-mediated diseases including AS and PsA.<\/jats:p>","DOI":"10.3390\/ijms262411801","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T08:21:43Z","timestamp":1765182103000},"page":"11801","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Kynurenic Acid Analog Attenuates the Production of Tumor Necrosis Factor-\u03b1, Calgranulins (S100A 8\/9 and S100A 12), and the Secretion of HNP1\u20133, and Stimulates the Production of Tumor Necrosis Factor-Stimulated Gene-6 (TSG-6) but Does Not Alter IL-17 Levels in Whole-Blood Cultures of Patients with Spondyloarthritis"],"prefix":"10.3390","volume":"26","author":[{"given":"Borisz","family":"Varga","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, University of Szeged, 6725 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0178-1243","authenticated-orcid":false,"given":"Gergely","family":"Toldi","sequence":"additional","affiliation":[{"name":"Liggins Institute, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e1szl\u00f3","family":"V\u00e9csei","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Szeged, 6725 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4729-2445","authenticated-orcid":false,"given":"Yvette","family":"M\u00e1ndi","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Attila","family":"Balog","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, University of Szeged, 6725 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1136\/ard.2010.133645","article-title":"The Assessment of SpondyloArthritis International Society Classification Criteria for Peripheral Spondyloarthritis and for Spondyloarthritis in General","volume":"70","author":"Rudwaleit","year":"2011","journal-title":"Ann. 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