Immunoregulatory cytokine profile in ischemic heart disease: association of IL-35, IL-17A and FOXP3 with clinical severity
R Alshehristani, H R Hassan, D J MohammadAbstract
Background
Immune-mediated inflammation plays a central role in atherosclerosis and clinical progression of ischemic heart disease (IHD). The balance between pro-inflammatory and regulatory immune pathways remains incompletely characterized in different coronary syndromes. This study investigated circulating interleukin-35 (IL-35), interleukin-17A (IL-17A), and FOXP3 in patients with varying IHD presentations.
Methods
A case–control observational study included 100 participants aged 25–85 years. Sixty patients with IHD were classified as stable angina (n=30), unstable angina (n=15), or myocardial infarction (n=15), and compared with 40 controls (with and without cardiovascular risk factors). Diagnosis was established according to guidelines from the European Society of Cardiology. Serum IL-35, IL-17A, FOXP3, and high-sensitivity C-reactive protein (hs-CRP) were quantified using ELISA. Statistical comparisons were performed using SPSS.
Results
hs-CRP levels were significantly elevated in IHD patients and showed a stepwise increase from stable angina to myocardial infarction (p<0.00001). IL-17A concentrations were markedly higher in myocardial infarction and unstable angina compared with stable angina and controls (p<0.00001). FOXP3 levels were significantly increased in unstable angina and myocardial infarction (p<0.001), indicating enhanced regulatory T-cell activation in advanced disease. In contrast, IL-35 concentrations were significantly reduced in IHD patients and in individuals with cardiovascular risk factors compared with healthy controls (p<0.00001). Combined biomarker profiles correlated with disease severity and inflammatory burden.
Conclusions
IHD is characterized by dysregulated immune homeostasis with reduced anti-inflammatory IL-35 and increased IL-17A, FOXP3, and hs-CRP. These biomarkers reflect disease severity across the spectrum of coronary syndromes and may represent complementary tools for risk stratification.
Clinical Implications
Immunological profiling may support inflammatory risk assessment and identify novel therapeutic targets aimed at restoring immune balance in IHD.Figure 1