| BackgroundAs the terminal stage of various cardiovascular diseases, chronic heart failure (CHF) is as malignant as many common types of cancer and associated with a comparable number of expected life-years lost. Many molecular, genetic, and biochemical pathways have been considered to participate in the development of CHF, while it is well recognized that neurohumoral activation plays an important role in it. Treatment withβ-blockers and angiotensin-converting enzyme inhibitors (ACEI) improves clinical symptoms and reduces overall mortality of CHF by antagonizing neurohumoral activation. However, mortality and morbidity remain substantial, underscoring the pathogenesis is not fully elucidated.Recent evidence suggests that immune activation and inflammation contribute to the pathogenesis of CHF, and T helper (Th) lymphocytes play critical roles in it. Th cells can be classified into two kinds according to the cyokines which they produce: Th1 and Th2. Thl cells participate in proinflammatory cellular immunity while Th2 cells downregulate inflammatory responses and regulate humoral immunity. As is well known, Th1/Th2 cytokine imbalance exists in patients with CHF despite various etiologies. What is more, as the fundamental medications for CHFβ-blockers and ACEI can act in the immune system and modulate the Thl/Th2 balance besides neurohumoral antagonism. Th17 cells which were recognized in 2005 are a new subset of Th lymphocytes distinct from Th1 and Th2 cells, and characterized by the production of IL-17. Th17 and/or IL-17 is associated with chronic inflammation and immunopathologic conditions, such as rheumatoid arthritis, psoriasis, inflammatory bowl diseases, systemic lupus erythematosus, tumor and coronary heart diseases. CD4+CD25+ regulatory T (Treg) cells are the most important subset of Treg cells and believed to maintain immunologic tolerance and control immune responses. Decreased numbers of Treg cells are related to impaired immune homeostasis and development of autoimmune diseases. The balance between Th17 cells and Treg cells maintains immune hemostasis, and otherwise will induce a series of inflammation responses. We hypothesized that the Th17/Treg balance was impaired in patients with CHF.ObjectiveTo explore the change and significance of Th17 cells and Treg cells in patients with CHF by analyzing the frequencies of Th17 cells and Treg cells in peripheral blood.Materials and Methods1. Patients77 patients with CHF were enrolled in this study. Age, sex, blood pressure, heart rate, NYHA heart function class, risk factor, etiology, medicine, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD) were recorded.18 healthy subjects were selected as controls.2. Exclusion criteriaInflammatory disease, autoimmune disease, recent myocardial infarction or unstable angina (within 3 months), rheumatic disease, hypothyroid disease, recent steroid therapy, advanced liver disease, renal failure, malignant disease and pregnancy were excluded.3. Methods According to LVEF 62 patients with symptoms of CHF whose plasma NT-proBNP level was increased were divided into 2 groups:heart failure with normal ejection fraction (HFNEF) group (LVEF>50%, NYHAⅡ～Ⅳ, n=28,16 men and 12 women, mean age 61.71±10.07) and heart failure with reduced ejection fraction (HFREF) group (LVEF<50%, NYHAⅡ～Ⅳ, n=34,24 men and 10 women, mean age 62.85±9.74).According to NYHA heart function class 49 patients with CHF (mainly the HFREF patients) were divided into 2 groups:CHF1 group (NYHAⅡ～Ⅳ,n=21,12 men and 9 women, mean age 61.48±8.46) and CHF2 group (NYHAⅢ～Ⅳ, n=28,20 men and 8 women, mean age 62.11±10.06).18 healthy donors constitute the control group.Peripheral Th17 and Treg frequencies were analyzed by flow cytometry. Plasma NT-proBNP levels were measured by Electrochemiluminescence immunoassay.4. Statistical analysisThe statistical analysis was performed with SPSS for Windows (version 16.0). Continuous values are expressed as mean±SD, and comparisons among the three groups were performed with either one-way ANOVA or the Kruskal-Wallis test. Categorical data are expressed as frequencies and percentages, andχ2 test was used for the analysis. Coefficients of correlation (r) were calculated by the Spearman rank test. P<0.05 was considered statistically significant.Results1. The frequencies of Th17 were significantly increased in patients with HFNEF compared with the controls (P<0.01). Moreover, the frequencies were higher in the HFREF group than the HFNEF group (P<0.01).The frequencies of Treg were obviously decreased in patients with HFNEF and HFREF compared with the controls (P<0.01). Moreover, there was significant difference between the HFNEF and HFREF group (P<0.01).The ratios of Th17/Treg were significantly higher in patients with HFNEF and HFREF than the controls (P<0.01). What is more, there was obvious difference between the HFNEF and HFREF group (P<0.01).2. The frequencies of Th17 showed positive correlation with plasma levels of NT-proBNP (r= 0.562, P<0.01), while the frequencies of Treg negatively correlated with plasma levels of NT-proBNP (r=-0.551, P<0.01).3. The frequencies of Th17 cells (CD4+IL-17+/CD4+T cells,%) were markedly increased in patients with poor heart function (CHF1 group and CHF2 group) than those with normal heart function (the healthy donors) (P<0.01), and the frequencies in CHF2 group were markedly increased than CHF1 group (P<0.01).The frequencies of Treg cells (CD4+CD25+Foxp3+/CD4+T cells,%) were markedly decreased in CHF1 group and CHF2 group than the healthy donors (P<0.01), and the frequencies in CHF2 group were markedly decreased than CHF1 group (P<0.05).The ratio of Th17/Treg increased while the heart function decreased. The ratio was markedly increased in patients with poor heart function (CHF1 group and CHF2 group) than those with normal heart function (the healthy donors)(P<0.01), and the ratio in CHF2 group was markedly increased than CHF1 group (P<0.01).ConclusionThe results indicate that the Th17/Treg imbalance exists in patients with CHF, suggesting the imbalance potentially plays a role in the pathogenesis, and the Th17/Treg balance may be a promising therapeutic approach in patients with CHF. |
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