Objective: This study aimed to investigate the link between circulating interleukin-18 (IL-18) levels and adult-onset Still’s disease (AOSD).
Methods: A thorough search was performed on MEDLINE, Embase, and Web of Science to find relevant articles. A meta-analysis was conducted to compare serum/plasma IL-18 levels in AOSD patients to those in control subjects.
Results: The meta-analysis included 13 studies with a total of 562 AOSD patients and 790 controls. The results showed a significant increase in IL-18 levels in the AOSD group compared to the control group (standard mean difference [SMD]=1.899, 95% confidence interval [CI]=1.078~2.720, p<0.001). When stratified by ethnicity, higher IL-18 levels were found in both Asian and European populations with AOSD. Subgroup analysis, regardless of variable adjustments, consistently indicated significantly higher IL-18 levels in the AOSD group. Significant elevations in IL-18 levels were observed in both small (n<50) and large groups (n>50), as well as in original and imputed data groups after data type stratification. Free IL-18 levels were significantly higher in the active group compared to the inactive group (SMD=0.900, 95% CI=0.532~1.268, p<0.001). The meta-analysis showed a positive correlation between IL-18 levels and ferritin (correlation coefficient=0.542, 95% CI=0.431~0.637, p<0.001) and C-reactive protein.
Conclusion: This meta-analysis demonstrated a significant increase in circulating IL-18 levels and a positive correlation between IL-18 levels and ferritin and C-reactive protein levels in patients with AOSD.

Keywords: Adult-onset Still’s disease, Interleukin-18, Ferritin, Polymorphism, Genetic, Meta-analysis