Correlations of expressions of peripheral blood regulatory T cells and related inflammatory factors with TOAST subtypes and infection risk in patients with acute cerebral infarction

Objective To explore the differences of degrees of immune inflammatory response in patients with different TOAST subtypes of acute cerebral infarction and their relations with infection risk after cerebral infarction. Methods One hundred and fifty-four patients with acute cerebral infarction who were free of detectable infection on admission, admitted to our hospital from October 2017 to June 2018, were recruited as patient group; according to TOAST subtypes, these patients were divided into large-artery atherosclerosis group (LAA, n=72), cardioembolic group (CE, n=38), and small-artery occlusion group (SAO, n=44); 45 healthy subjects enrolled at the same period were selected as control group. Fasting blood samples were taken on the next day of admission or during physical examination. Treg% (percentage of CD4+CD25+CD127[low] regulatory T cells [Treg] in CD4+ lymphocytes) was measured by flow cytometry. Interleukin (IL)-6, IL-10, and hypersensitive C-reactive protein (hsCRP) levels were measured by ELISA or Turbidimetric inhibition immuno assay. Spearman correlation analysis was performed to investigate the relations of Treg% and related inflammatory factors with TOAST subtypes of acute cerebral infarction and post-stroke infection risk. Receiver operating characteristic (ROC) curve was used to analyze the predictive values of Treg% and inflammatory factors in post-stroke infection. Univariate Logistic regression analysis and multivariate Logistic regression analysis were used to screen the risk factors of infection after cerebral infarction. Results (1) Treg% in LAA group was significantly lower than that in control group (P<0.05), and Treg% in CE group was statistically higher than that in control group (P<0.05); patients in the LAA and CE groups had significantly higher IL-6 and hsCRP levels as compared with those in the control group (P<0.05); patients in the LAA, CE and SAO groups had significantly lower IL-10 level than those in the control group (P<0.05); patients in the LAA and SAO groups had significantly decreased IL-6 and IL-10 levels as compared with those in the CE group (P<0.05); patients in the SAO group had significantly lower hsCRP level as compared with those in the CE group (P<0.05). Spearman correlation analysis showed that Treg% was negatively correlated with LAA (rs=-0.488, P=0.000) and positively correlated with CE and SAO (rs=0.355, P=0.000; rs=0.200, P= 0.013); the levels of IL-6, IL-10 and hsCRP were positively correlated with CE (rs=0.578, P=0.000; rs= 0.508, P=0.000; rs=0.299, P=0.015), and negatively correlated with SAO (rs=-0.404, P=0.001; rs=0.394, P=0.001; rs=0.308, P=0.012). (2) There were 36 patients who developed infection associated with cerebral infarction in the patient group; as compared with those in the non-infection group, Treg%, IL-6, IL-10 and hsCRP levels in the infection group were significantly increased (P<0.05); Spearman correlation analysis showed that Treg% and hsCRP were positively correlated with infection after cerebral infarction (rs= 0.305, P= 0.007; rs=0.653, P=0.000). The area under the curve of hsCRP for prediction of post-stroke infection was 0.943 (95% confidence interval [CI]: 0.895-0.992, P=0.000), that of Treg% was 0.707 (95%CI: 0.548-0.866, P=0.008), and that of combination of hsCRP and Treg% was 0.958 (95%CI: 0.918-0.998, P=0.000). (3) Multivariate Logistic regression analysis showed that hsCRP was an independent risk factor for post-infarction infection (P<0.05). Conclusions There are differences in the degrees of immune inflammatory response among patients with different TOAST subtypes of acute cerebral infarction. Treg% and hsCRP can be used as early warning markers of infection after cerebral infarction. Key words: Acute cerebral infarction; TOAST subtype; Post-stroke infection; Regulatory T cell; Interleukin-6; Interleukin-10; Hypersensitive C-reactive protein