J Rheum Dis.  2025 Jan;32(1):48-56. 10.4078/jrd.2024.0095.

Associations between circulating interleukin-18 levels and adult-onset Still’s disease: a meta-analysis

• Lee YH
• Song GG

• KMID: 2562659
• DOI: http://doi.org/10.4078/jrd.2024.0095

Abstract

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.

Keyword

Adult-onset Still’s disease; Interleukin-18; Ferritin; Polymorphism; Genetic; Meta-analysis

Figure

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  Figure 1 Flowchart depicting the study selection process for the meta-analysis.

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  Figure 2 Meta-analysis illustrating the relationship between circulating IL-18 levels and AOSD. IL-18: interleukin-18, AOSD: adult-onset Still’s disease, CI: confidence interval.

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  Figure 3 Meta-analysis showing the correlation coefficient between circulating IL-18 levels and ferritin (A), as well as CRP (B). IL-18: interleukin-18, CRP: C-reactive protein, CI: confidence interval.

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