{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:30:08Z","timestamp":1785407408338,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T00:00:00Z","timestamp":1777075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Trakya University Scientific Research Projects Unit","award":["2024\/11"],"award-info":[{"award-number":["2024\/11"]}]},{"award":["2024\/11"],"award-info":[{"award-number":["2024\/11"]}],"id":[{"id":"https:\/\/ror.org\/00xa0xn82","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Cytokine-mediated immune dysregulation contributes to the heterogeneity of multiple sclerosis (MS). Interleukin-18 (IL-18) and interleukin-8 (IL-8) are involved in distinct inflammatory pathways; however, their genetic contributions to disease susceptibility and radiological activity remain incompletely defined. Methods: In this study, 98 relapsing\u2013remitting MS (RRMS) patients and 98 healthy controls were genotyped for IL-18 and IL-8 variations using PCR-based methods. Clinical data and MRI findings were analyzed in the MS cohort. Associations with disease susceptibility, clinical severity (EDSS), and MRI activity were evaluated using regression analyses. Results: IL-18 (\u2212137 G\/C) and IL-8 variations were significantly associated with MS susceptibility. The G allele of IL-18 (\u2212137), the T allele of IL-8 (\u2212251), and the C allele of IL-8 (+781) were more frequent in MS patients. No significant associations were observed between cytokine variations and clinical severity measures. However, IL-18 (\u2212137) variation was significantly associated with higher baseline MRI lesion burden, with C allele carriers showing increased lesion counts. In addition, IL-8 (\u2212251 AA genotype) was independently associated with increased annual lesion development. These findings were confirmed in multivariable regression analyses. Conclusions: IL-18 and IL-8 gene variations contribute to MS through distinct but complementary mechanisms. IL-18 appears to be primarily involved in disease susceptibility and baseline inflammatory burden, whereas IL-8 is more closely associated with ongoing radiological activity. These results highlight the importance of integrating genetic and imaging biomarkers to better understand disease heterogeneity in MS.<\/jats:p>","DOI":"10.3390\/jcm15093281","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T09:55:39Z","timestamp":1777370139000},"page":"3281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential Roles of IL-18 and IL-8 Gene Variations in Multiple Sclerosis: Associations with Susceptibility and MRI Disease Activity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9608-9278","authenticated-orcid":false,"given":"Sezgin","family":"Kehaya","sequence":"first","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Trakya University, Edirne 22030, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8412-091X","authenticated-orcid":false,"given":"Arzu","family":"Ay","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Trakya University, Edirne 22030, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3745-8838","authenticated-orcid":false,"given":"Nevra","family":"Alkanli","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Hali\u00e7 University, Istanbul 34060, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3631-4447","authenticated-orcid":false,"given":"Ayse Nur","family":"Cesme","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Trakya University, Edirne 22030, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e70135","DOI":"10.1111\/cns.70135","article-title":"Microglial Mayhem: NLRP3 Inflammasome\u2019s Role in Multiple Sclerosis Pathology","volume":"30","author":"Fan","year":"2024","journal-title":"CNS Neurosci. 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