Th2 predominant immune response prevails in patients with coronary artery ectasia and non-obstructive coronary artery disease

Purpose: T helper (Th) lymphocytes are present in significant numbers in the atherosclerotic plaque. Even though coronary artery ectasia (CAE), a variant of coronary atherosclerosis, has been associated with increased levels of inflammatory markers, the underlying mechanism that determines the role of inflammation in CAE remains controversial. We evaluated the hypothesis that CAE might be associated with a specific pattern of Th lymphocyte activation by measuring the Th-1 cytokine, interleukin-2 (IL-2) and the Th-2 cytokines, interleukin-4 (IL-4) and interleukin-6 (IL-6) in patients with CAE, obstructive coronary artery disease (CAD) and normal individuals. Methods: Plasma levels of IL-2, IL-4 and IL-6 were measured in 74 patients (56 males, mean age: 63.3±9.8 years) undergoing an elective cardiac catheterization due to symptoms of angina pectoris and positive or equivocal results during non-invasive cardiac ischaemia screening: 34 patients had CAE and non-obstructive CAD (group A), 22 had obstructive CAD (group B) and 18 had normal coronary arteries (group C). Results: Group A had significantly higher levels of serum IL-4 compared to group B (mean±SD: 7.1±1.0 pg/ml vs. 3.8±0.8 pg/ml, p<0.001) and group C (mean±SD: 7.1±1.0 pg/ml vs. 6.1±1.4 pg/ml, p=0.006). In contrast, Group A had markedly lower levels of serum IL-2 compared to group B (mean±SD: 13.8±3.3 pg/ml vs. 28.4±5.9 pg/ml, p<0.001) and group C (mean±SD: 13.8±3.3 pg/ml vs. 20.1±6.9 pg/ml, p<0.001). Serum IL-4 was higher in group C compared to group B (mean±SD: 6.1±1.4 pg/ml vs. 3.8±0.8 pg/ml, p<0.001), whereas group B had higher serum IL-2 than group C (mean±SD: 28.4±5.9 pg/ml vs. 20.1±6.9 pg/ml, p<0.001). Serum IL-6 levels were significantly higher in group A and B compared to group C [median (IQR): 6.7 (2.8-11.7) pg/ml and 8.2 (2.1-14.0) pg/ml vs. 1.8 (1.2-2.3) pg/ml, respectively, p<0.001 for both comparisons], whilst the corresponding levels were comparable between group A and B (p=0.8). Multivariate logistic regression analysis showed that higher levels of IL-4 and lower levels of IL-2 were the strongest independent predictors associated with the incidence of CAE (OR: 3.846, CI:1.677-8.822, p=0.001 and OR:0.567, CI:0.387-0.831, p=0.004, respectively). Conclusions: Our data demonstrates for the first time that Th-2 inflammatory response, exhibited through increased serum levels of IL-4 and low serum IL-2, constitutes a fundamental feature of CAE phenotype.