Changes Of Th1/Th2 Cytokines In The Peripheral Blood Of Patients With Acute Coronary Syndromes And The Effect Of Atorvastatin Intervence

ObjectiveIn recent years,a lot of studies have showed that inflammation and immune mechanism take part in the pathophysiological process of atherosclerosis plague aggression which lead to the genesis and development of ACS. Many kinds of cytokines play important roles in the course.In this study, we measured and compared serum concentration of Th1/Th2 cytokines in patients with different clinical kinds of coronary heart disease(CHD) to investigate the effect of these cytokines on the genesis and development of ACS and evaluate the effect of atovastatin intervence.MethodFrom May.2008 to April.2009, altogether 120 cases of hospitalized patients who underwent coronary angiography were included in this study.They were divided into 4 groups: (1) Patients with acute myocardial infarction (AMI) were 22 cases, 11 of them were male, and 11 were female. The average age was 59.6±8.5 years old. All of them demonstrated ST elevation on electrocardiogram and were within 24 hours of onset. (2) Patients with unstable angina pectoris (UAP) were 42 cases, 22 of them were male, and 20 were female. The average age was 59.1±8.8 years old; (3) Patients with stable angina pectoris (SAP) were 34 cases, 18 of them were male, and 16 were female. The average age was 61.1±8.1 years old; (4)The controls were 22 cases, 12 of them were male, and 10 were female. The average age was 60.1±8.6 years old. Their angiographic images were normal. All patients (with or without coronary heart disease) were performed coronary angiography. The severity of pathological changes of the coronary artery was assessed by the number of diseased coronary branches and Gensini's score.According to the results of CAG, the 120 patients were divided into two groups: CHD group(n=98) and non-CHD group as control(n=22).The CHD patients were further divided into subgroups according to the the number of diseased coronary branches and Gensini's score. 42 patients with UAP were divided into two groups by cardiac events including acute myocardial infarction, sudden cardiac death and refractory angina pectoris: cardiac event group 16 subjects, no-cardiac event group 26 subjects. The levels of HGF and VEGF were measured. Blood samples were obtained from venous at the next morning after admission of the patients of SAP,UAP and control groups. The blood samples of patients of AMI group were obtained immediately after admission. The lipoprotein,glucose of blood sample were examined. The concerntration of plasma IFN-γ,IL-4,IL-2 and IL-10 were evaluated by ELISA. Heparinized blood samples were immediately centrifuged and plasma was frozen and kept at–70°C before ebaluation. Plasma cytokine (IFN-γ,IL-2,IL-4 andIL-10) concentrations were measured by ELISA. At last,we performed a follow up of statins treatment of three months to observe the changes of items above,and affirmed the conclusion that statins have regulation effect on immunologyResults:1) Patient characteristics. There were no significant differences in age, gender, lipid, blood glucose, hypertension, or frequency of smoking in patients with SA, UA or MI.2) Th1 cells and Th2 related cytokines among the groups. The level of IFN-γand IL-2 were elevated in patients with UA and MI compared to those with SA and controls (p<0.05). Difference in concentrations of IFN-γand IL-2 between the SA and control or the UA and AMI groups was not significant (p>0.05). The level of IL-4 and IL-10 decreased in patients with UA and MI compared to those with SA and controls (p<0.05). Difference in concentrations of IL-4 and IL-10 between the SA and control or the UA and AMI groups was not significant (p>0.05).3) Plasma Th1/Th2 cytokines levels were not correlated with severing of coronary artery disease. Association of the types of lesions with the level of Th1/Th2 cytokines in the UAP group: Compared with the type I lesion, patients with type II lesions showed higher in-gate percentage of Th1 cytokines. and lower concentration of Th2 cytokines 4) Among patients with UAP,the level of IFN-γand IL-2 was highest in Braunwald III,Or the contray the level of IL-4 and IL-10 was lowest.5) Among patients with UAP , the level of IFN-γand IL-2 were significantly higher in cardiac event group than no-cardiac events group(P <0.05).The levels of IL-10 and IL-4 were significantly lower in cardiac event group than no-cardiac events group (P <0.05).6) Effect of atorvastatin on the serum level of Thl/Th2 cytokines in all of groups: The serum level of IL-4 or IL-10 in SAP,UAP and AMI groups was not significant difference compared with three months before(P>0.05). The serum level of IFN-γand IL-2 in SAP,UAP and AMI groups was significant decrease in UAP and AMI groups compared with three months before(P<0.05).ConclusionsOur study provided the direct proof that Th1 cells related cytokines expansion and Th2 cells related cytokines reduction are consistent with the development of plaques instability. The imbalance between Th1 cells and Th2 cells might contribute to atherosclerotic plaque destabilization in patients with CAD. These results suggested a new point for the modulation of atherosclerosis and may shed light on the stabilization of vulnerable plaque. Plasma Thl/Th2 cytokines levels were not correlated with of Coronary Artery Disease.Additional, Plasma Thl/Th2 cytokines levels may not be a new markers for surveillance on coronary artery disease stenonsis. The levels of Th1 cells related cytokines were significantly higher in cardiac event group than no-cardiac event group; these indicate that there are correlation between the levels of Th1 cells related cytokines and unstable angina.Our results suggested that atorvastatin can suppress the activation of Th1 related cytokines and improve the imbalance of Th1 /Th2 in ACS.