A Preliminary Study On Serum Expression Level Of IL-27and Their Significances In The Patients With Chronic Heart Failure

Chronic heart failure (Chronic heart failure, CHF) is a common cardiovascular disease. It is a group of syndromes caused by vent ricular filling and (or) the damage of ejection ability, which are caused by various cardiac structure or functional diseases, and CHF is the end stage of heart disease. In recent years, though the incidence of rheumatic heart disease has declined, the incidence of coronary heart disease, hypertension and other diseases gradually increased with the economic development and the improvement of people’s living standards, and it has a accelerated trend, leading to the incidence of chronic heart failure is still on an upward trend, which seriously reduces the quality of people’s lives, and also exacerbates the public health burden in China. According to the latest European Heart Failure Prevention Guide, the incidence rate of adult heart failure in developed countries is1-2%, but the incidence of the population over the age of70is more than10%; while in the past four decades in our country, death toll caused by heart failure increased six-fold. Exploring the pathogenesis of chronic heart failure actively, early intervention, diagnosis and treatment, and to reduce its morbidity and mortality have become urgent problems to solve in the field of World Health.Before the1990s,60-70%patients with chronic heart failure died within5years after they had diagnosis on the disease, and they required hospitalization because of frequent exacerbations of heart failure, which led to hospitalization for heart failure in many country had become popular. Chronic heart failure is a progressive disease, once it starts, the heart function of the patients with heart failure will be damaged by the continuous development of myocardial remodeling mechanisms even if there are no new myocardial injury. The sympathetic nervous system and the reflex and excitability of renin-angiotensin-aldosterone system (RAAS) will increase, and at the same time a variety of endogenous neurohormone will be activated after the decline in heart function caused by the initial myocardial injury; the activation of chronic neuroendocrine system will lead to myocardial remodeling and myocardial fibrosis, and thereby increases myocardial injury and cardiac dysfunction, which in turn lead to further functional disorders and further activation of neuroendocrine, thus creating a vicious cycle. Therefore, the key to the treatment of heart failure is blocking this vicious cycle. The treatment of chronic heart failure has a very noteworthy change since1990s. The change is from the short-term hemodynamic/pharmacological measures to long-term and reparative strategies. The goals of heart failure treatment should be not only improving symptoms and improving quality of life, but also preventing and delaying the development of myocardial remodeling aimed at the mechanism of myocardial remodeling, thereby reducing mortality and hospitalization rates of heart failure. It found that using the drugs of β-blockers and angiotensin-converting enzyme inhibitors (ACEI) to treat patients with chronic heart failure in clinical application, their quality of life and prognosis has obvious improvement, but epidemiological studies have shown that heart failure still has a higher morbidity and mortality, suggesting that some mechanism of heart failure is still undiscovered and not corrected by clinical treatment. In recent years, the role of inflammatory cytokines in the pathogenesis of CHF has become a hot topic. With in-depth research, it finds that a variety of inflammatory cytokines have close relationship with CHF. Studies have shown that in the plasma of patients with CHF, IL-1, IL-6, IL-18, and TNF-a and Fas ligand was significantly higher, while elevated inflammatory factors has a close relationship with cardiac function classification, left ventricular function and CHF poor prognosis. And it is also confirmed in a number of animal models that cytokines and other inflammatory mediators play an important role in the pathogenesis of CHF. Inflammatory cytokines can not only act on myocardial cells and fibroblasts directly and affect cardiac function caused by myocardial hypertrophy and fibrosis, but also can act on intracellular transport of calcium and signal transduction to damage the myocardial contractile function. In addition, inflammatory factors may also exacerbate the development of CHF through a series of indirect effects, such as acting on hematopoietic cells in the bone marrow to bring secondary anemia. But on the other hand, the results of immunotherapy to the patients with heart failure were frustrating. Many interventions were terminated because the result was ineffective or complications were too heavy. This is due to the complexity of the inflammatory immune system; on the other hand, people also do not concretely understand the role of inflammatory immune in chronic heart failure. Researchers should make more efforts in the relevant areas. Currently, there are many researches for pro-inflammatory cytokines, but the researches for the role of anti-inflammatory cytokines in CHF are less.Newly discovered IL-27belongs to IL-6/IL-12family, which is a heterodimer composed by EB virus induced gene3(EB virus induce gene3, EBI3) and p28. It is mainly produced by dendritic cells, macrophages, monocytes and other antigen-presenting cells; it will secrete IL-27when the Toll-like receptors (TLRs) on the surface of is stimulated by pathogen-associated molecular pattern (PAMP). IL-27receptor (IL-27R) is a heterodimer formed by WSX-1(also known as T-cell cytokine receptor, TCCR) and glycoprotein130(glycoprotein130, gp130). Unlike the cells of producing IL-27, its receptors are widely distributed in a variety of cells in the body, such as naive T cells, natural killer cells (NK cells), monocytes, mast cells, endothelial cells, keratinocytes, activated B cells, Langerhans cells (Langerhan cells) and dendritic cells, etc. Interleukin27specifically binds to its receptor, through gp130, and activates different JAK/STAT (janus kinase/signal transducer and activator oftranscription) pathway in a variety of different cell, causing specific biological responses, which possesses a wide range of two-way adjustment effect on pro-inflammatory and anti-inflammatory. Hiroki Yoshida et.al found that relative to wild-type mice, the production of IFN-γ in WSX-1-/-mice significantly weakened and the WSX-1-/-mice were more susceptible to Lishi Man protozo. In addition, interleukin-27promotes the production of IL-1β, TNF-α, IL-18, IL-12, chemotactic cytokine, adhesion molecules and other proinflammatory cytokines. These results suggest that IL-27can promote inflammation and immune responses. A growing number of studies found that IL-27can also suppress inflammation and immune response. Compared with the wild-type mice, WSX-1-/-mice infected with Trypanosoma cruzi produce excessive IFN-y, resulting in immune response going out of control and leading to cytokine-mediated liver damage. CD4+T lymphocytes isolated from WSX-1-/-mice infected with Trypanosoma cruzi can secrete a large variety of pro-inflammatory cytokines, such as IL-6and TNF-a. In allergic airway hyper-responsiveness model, WSX-1-/-mice also secrete excessive amounts of cytokines. Vitro studies have also found that IL-27can suppress the secretion of the proinflammatory cytokines by T lymphocyte. The two-way adjustment of IL-27to inflammatory immune makes it become a hotspot in the research of autoimmune disease, cancer and infectious disease. The role of IL-27in the pathogenesis of vertebral insects, Lishi Man protozoa and Mycobacterium tuberculosis infectious diseases Crohn’s disease and other autoimmune diseases as well as cancer has been gradually revealed, while studies have shown that IL-27plays anti-inflammatory, immunosuppressive, anti-angiogenesis and anti-tumor effect. The preliminary studies of the experimental group also showed that IL-27levels in peripheral blood of patients with coronary heart disease went up and it implies that IL-27levels may be associated with the severity of coronary heart disease. How is the role of IL-27in the pathogenesis of chronic heart failure? Our research group plan to analyze comparatively the IL-27level in plasma between chronic heart failure patients and healthy subjects, and to evaluate its relationship with NT-proBNP, CRP, and left ventricular ejection fraction.Methods:Select a total of64cases of heart failure patients from July2012to September2012as research subjects who were hospitalized in Department of Cardiology, Zhujiang Hospital, Southern Medical University. Include coronary heart disease,30cases, and22cases of hypertensive heart disease,6cases of rheumatic heart disease, and6cases of dilated cardiomyopathy. Classify cardiac function according to New York Heart Association (NYHA), cardiac function group Ⅱ(24cases), cardiac function group Ⅲ(19cases), cardiac function group Ⅳ (21cases). The patients suffering from a variety of pathogens infection, autoimmune diseases, cancer, allergies, blood diseases, stroke, acute myocardial infarction and other serious system diseases as well as the patients using anti-inflammatory or immunosuppressant were excluded. Select20examinations in our clinic during the same period as the control group, including10male and10female. There were not significantly different between the groups in age and gender. Collect the general clinical data for all patients, and detect IL-27content in plasma for all selected patients using the method of enzyme-linked immunosorbent assay (ELISA). Detect hs-CRP and NT-proBNP respectively using the method of Turbidimetric immunoassay and direct chemiluminescence. Statistical analysis was performed by SPSS13.0statistical software.Results:1.General clinical data the difference was not statistically significant (P>0.05) in each group in terms of gender, age, blood lipids and glucose levels.2.The Plasma level of IL-27, hsCRP, NT-proBNP and LVEF in different groups CHF group ((0.284±0.186ng/ml) ng/ml) in plasma IL-27level was significantly lower than the control group ((0.746±0.414) ng/ml), the difference was statistically significant (P<0.05); IL-27level decreased further with cardiac function in NYHA classification level rising, and the difference was statistically significant (P<0.05). Pairwise comparison results show severe heart failure (cardiac group Ⅲ,Ⅳ) was lower than that of the control group (P<0.05), but no statistically significant differences in cardiac function Ⅱ and control group. CHF group in plasma hsCRP levels are significantly higher than that in the control group, and the difference was statistically significant (P<0.05); the hsCRP level increased further with cardiac function in NYHA classification levels rising, and the difference was statistically significant (P<0.05). Pairwise comparison results show severe heart failure (cardiac function Ⅲ,Ⅳ) was higher than that of the control group (P<0.05). The difference of plasma NT-proBNP and LVEF level in CHF group and the control group was statistically significant (P<0.05); heart failure group in NT-proBNP levels are significantly higher than that in the control group, and NT-proBNP levels elevated with the classification rising between different cardiac functional grading subgroups, and the difference was statistically significant (P<0.05). LVEF level in the heart failure group was significantly lower than that in the control group. LVEF level decreased with the classification rising, and the difference was also statistically significant (P<0.05). 3.Correlation analysis of IL-27and hsCRP, NT-proBNP and LVEF in all objects of this study.Analyze the correlation between hsCRP level and IL-27level of64patients, and the analysis showed that plasma IL-27level was negatively correlated with hsCRP (r=-0.54,P<0.05).Analyze the correlation between IL-27level and NT-proBNP level of64patients, and the analysis showed that plasma IL-27levels was negatively correlated with NT-proBNP (r=-0.47, P<0.05).Analyze the correlation between IL-27level and LVEF level, and the analysis showed that plasma IL-27level was positively correlated with LVEF (r=0.71, P<0.05).Conclusion:IL-27level in peripheral blood of patients with chronic heart failure significantly reduced compared with the control group, and IL-27levels was negatively correlated with hsCRP and NT-proBNP while positively correlated with LVEF level. This suggested that IL-27play an important role in the evaluation of the severity of CHF.