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article · Egyptian Rheumatology and Rehabilitation

Serum interleukin-18 as a biomarker of disease activity and interstitial lung disease in rheumatoid arthritis

2025Open accessAlexandria University

Abstract

Rheumatoid arthritis (RA) is a chronic systemic condition, marked by inflammatory alterations of the synovial tissue in joints, cartilage, and bone. Interleukin-18 (IL-18), a member of the IL-1 family, is a significant pro-inflammatory cytokine that could contribute to the development of RA. We aimed to measure the serum IL-18 level in patients with RA and correlate its level with different disease characteristics, disease activity, and the presence of interstitial lung disease. A case-control study was conducted on 121 subjects: 60 adult RA patients who met the 2010 ACR/EULAR criteria for RA, and 61 age and sex-matched healthy controls. All patients have undergone a comprehensive evaluation, including a history and physical examination, a disease activity score (DAS28), and chest x-ray and high-resolution computed tomography of the chest. Laboratory investigations included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), and serum IL-18 level. The 60 RA patients were 17 males (28.3%) and 43 females (71.7%) with a mean age of 45.13 ± 13.70 years, and disease duration was 8.86 ± 7.91 years. Interstitial lung disease related to RA was found in 8 RA patients (13.3%). The mean serum IL-18 level among RA patients was (652.3 ± 245.2 pg/mL), while in the control group it was (323.1 ± 106.6 pg/mL) with a statistically significant difference (p < 0.001). Moreover, the mean level of serum IL-18 in RA patients with interstitial lung disease (ILD) was (896.4 ± 162.7 pg/mL), and this was statistically significant when compared to RA patients without ILD (p = 0.001). There was a significant positive correlation between IL-18 and ESR, CRP, RF, and DAS28 (p = 0.013, p = 0.010, p < 0.001, and p < 0.001, respectively). Serum IL-18 was significantly higher in RA patients than in controls; furthermore, it was positively correlated with inflammatory markers and disease activity. An increased IL-18 level was associated with the presence of ILD; thus, IL-18 could be a potential biomarker for assessing RA activity and associated ILD.

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DOI: 10.1186/s43166-025-00364-y

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