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Background <p>Rheumatoid arthritis (RA) confers 50–70% higher cardiovascular (CV) risk due to inflammation and dyslipidemia. Carotid intima-media thickness (CIMT) marks subclinical atherosclerosis, but the link with specific cytokines is unclear. The study aims to evaluate IL-15, IL-18, and IL-33 as markers of RA disease activity and examine their association with IMT at four sites [common carotid artery (CCA), brachiocephalic trunk (BCT), carotid bulb, and internal carotid artery (ICA)] as site-specific atherosclerosis markers.</p> Methods <p>This cross-sectional study measured serum cytokines, lipid profiles, and IMT at four sites in 100 Egyptian RA patients and 50 healthy controls. Disease activity (DAS28), rheumatoid factor, anti-CCP status, and CV risk factors were assessed. Multiple logistic regression and ROC analysis evaluated cytokine utility for predicting CCA- and BCT-IMT alterations.</p> Results <p>All cytokines were significantly elevated in RA (<i>p</i> &lt; 0.0001). IL-15 correlated most strongly with DAS28 (<i>r</i> = 0.873, <i>p</i> &lt; 0.001). BCT-IMT was higher in RF+ patients (<i>p</i> &lt; 0.001), unlike other IMT sites. BCT-IMT correlated strongly with traditional risk factors (TC, TG) and all cytokines: IL-15 (β = 0.0054, <i>p</i> &lt; 0.001), IL-18 (β = 0.0027, <i>p</i> &lt; 0.001), IL-33 (β = 0.0032, <i>p</i> &lt; 0.041). CCA-IMT was linked only to HDL, LDL, and IL-15 (β = 0.0052, <i>p</i> &lt; 0.001). Patients with thickened BCT-IMT differed in lipid profiles and cytokine levels. ROC analysis showed IL-15 had the highest diagnostic accuracy for RA and BCT-IMT [AUC = 0.97 (95% CI: 0.961–0.995) and 0.98 (95% CI: 0.968- 1.00)], followed by IL-18 [AUC = 0.91 (95% CI: 0.870–0.965) and 0.92 (95% CI: 0.877–0.970)] and IL-33 [AUC = 0.89 (95% CI: 0.838–0.950) and 0.97 (95% CI: 0.949–0.995)].</p> Conclusions <p>IL-15 is strongly correlated with RA-associated atherosclerosis, particularly at the BCT, reflecting its potential dual inflammatory and lipid-modulatory role. BCT-IMT appears more sensitive to RA-specific vascular damage than CCA-IMT. Combined IL-15 and BCT-IMT assessment may improve early CV risk prediction in RA.</p>

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Association of interleukin-15, -18 and − 33 levels with site-specific subclinical atherosclerosis in rheumatoid arthritis patients

  • 期刊论文

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  • 发表日期：

    2026年6月16日

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  • Eman F. Hamza,
  • Hala M. Raslan,
  • Azza M. El Amir,
  • Noha A. Mahana,
  • Neveen A. Madbouly

摘要

Background

Rheumatoid arthritis (RA) confers 50–70% higher cardiovascular (CV) risk due to inflammation and dyslipidemia. Carotid intima-media thickness (CIMT) marks subclinical atherosclerosis, but the link with specific cytokines is unclear. The study aims to evaluate IL-15, IL-18, and IL-33 as markers of RA disease activity and examine their association with IMT at four sites [common carotid artery (CCA), brachiocephalic trunk (BCT), carotid bulb, and internal carotid artery (ICA)] as site-specific atherosclerosis markers.

Methods

This cross-sectional study measured serum cytokines, lipid profiles, and IMT at four sites in 100 Egyptian RA patients and 50 healthy controls. Disease activity (DAS28), rheumatoid factor, anti-CCP status, and CV risk factors were assessed. Multiple logistic regression and ROC analysis evaluated cytokine utility for predicting CCA- and BCT-IMT alterations.

Results

All cytokines were significantly elevated in RA (p < 0.0001). IL-15 correlated most strongly with DAS28 (r = 0.873, p < 0.001). BCT-IMT was higher in RF+ patients (p < 0.001), unlike other IMT sites. BCT-IMT correlated strongly with traditional risk factors (TC, TG) and all cytokines: IL-15 (β = 0.0054, p < 0.001), IL-18 (β = 0.0027, p < 0.001), IL-33 (β = 0.0032, p < 0.041). CCA-IMT was linked only to HDL, LDL, and IL-15 (β = 0.0052, p < 0.001). Patients with thickened BCT-IMT differed in lipid profiles and cytokine levels. ROC analysis showed IL-15 had the highest diagnostic accuracy for RA and BCT-IMT [AUC = 0.97 (95% CI: 0.961–0.995) and 0.98 (95% CI: 0.968- 1.00)], followed by IL-18 [AUC = 0.91 (95% CI: 0.870–0.965) and 0.92 (95% CI: 0.877–0.970)] and IL-33 [AUC = 0.89 (95% CI: 0.838–0.950) and 0.97 (95% CI: 0.949–0.995)].

Conclusions

IL-15 is strongly correlated with RA-associated atherosclerosis, particularly at the BCT, reflecting its potential dual inflammatory and lipid-modulatory role. BCT-IMT appears more sensitive to RA-specific vascular damage than CCA-IMT. Combined IL-15 and BCT-IMT assessment may improve early CV risk prediction in RA.