Serum Levels of the Proinflammatory Cytokines IL-6, IL-16, IL-18, and IL-36 in Patients with Multiple Sclerosis from the Western Region of Saudi Arabia: Associations with Disease Duration and Disability

Abstract

Background: Systemic inflammation contributes to the pathobiology of multiple sclerosis (MS), yet serum biomarker data from Middle Eastern populations remain limited. This study evaluated serum levels of IL-6, IL-16, IL-18, and IL-36 in Saudi adults with MS compared with matched healthy controls and examined associations with disease duration, phenotype, treatment, and disability. Methods: This single-center, cross-sectional, matched case–control study enrolled 26 MS patients and 26 age- and sex-matched controls. Serum cytokines were measured by ELISA. Disability was assessed using EDSS and the Timed 25-Foot Walk (T25FW). Matched comparisons used Wilcoxon signed-rank tests; subgroup comparisons used Wilcoxon rank-sum or Kruskal–Wallis tests; associations used Spearman’s correlation. Results: No correction for multiple comparisons was applied given the exploratory design. All four interleukins were higher in MS patients than in controls (p < 0.001). Age correlated with EDSS (r = 0.573, p = 0.002) and T25FW (r = 0.464, p = 0.014). Only IL-6 showed a notable correlation with disability, with T25FW (r = 0.53, p = 0.008) and, weaker, EDSS (r = 0.38, p = 0.052); IL-18 showed a weak, non-significant correlation with T25FW (r = 0.35, p = 0.126); IL-16 and IL-36 showed no relevant associations. IL-16 was higher in newly diagnosed than in long-standing cases (p = 0.012); no differences by phenotype or treatment were observed for any marker. Conclusions: Serum IL-6, IL-16, IL-18, and IL-36 were elevated in Saudi MS patients versus controls. IL-6 alone showed a modest, unadjusted association with disability, supporting its evaluation as a candidate biomarker in larger, longitudinal, covariate-adjusted cohorts. These findings are hypothesis-generating and should not be interpreted as evidence of independent or clinically actionable biomarker utility.