Study Of Chronic Obstructive Pulmonary Disease's Systemic Effects And The Level Of NF-κB And Inflammatory Factors

Chronic Obstructive Pulmonary Disease (COPD) has become an important public health issue. Now COPD ranks as the 4th leading cause of death in the world. WHO Global Burden of Disease study shows that by 2020 COPD will be second only to ischemic heart disease, cerebrovascular disease, cause of death worldwide ranking first three. At present, there are about 43,000,000 patients with chronic obstructive pulmonary disease in China. The incidence of COPD is rising increasingly, and the lung function in patients is gradually deteriorating, at the same time there is physiological dysfunction,decreased mobility,disability and other long-term serious adverse effects. The pathogenesis of COPD has not yet fully understood . Now widely recognize that COPD is characterized by chronic inflammation of airway, lung parenchyma and pulmonary blood vessels. In different parts of the lung ,there are alveolar macrophages, T lymphocytes (especially CD8+) and neutrophil increasing , and in some patients there are eosinophils increasing. Most studies confirm that activated inflammatory cells release a variety of inflammatory mediators , and these inflammatory mediators play an important role in the process of occurrence and development of COPD. Transcription factor NF-κB is research focus of the inflammatory response. A large number of scientific data confirm that, in acute phase of inflammatory response, The activation of NF-κB regulates a variety of transcription of inflammatory factors and then forms inflammatory cascade effect .Objective: Detect the expression level of NF-κB,TNF-α,IL-8,IL-6,IL-1 in the serum of patients with stable COPD,analysis their relevance and the relationship between them and lung function,activity endurance in patients. Preliminarily study the clinical significance and potential applications of NF-κB,TNF-α,IL-8,IL-6,IL-1 in elderly patients with stable COPD.Methords: Patients were from Department of Respiratory Medicine Inpatient of Henan Province People's Hospital (December 2008- December2009) and the normal control group were from clinic healthy individuals . According to the Guideline for chronic obstructive pulmonary disease of Respiratory Branch of Chinese Medical Association, screend patients with stable COPD. Patients and health people made pulmonary function test and 6-minute walk test . Collected 6ml fasting peripheral venous blood from patients(n=30) and people of normal control group(n=30). After the separation of serum, TNF-α,IL-8,IL-6,IL-1 were determined by ELISA, and then mononuclear cells were isolated from the remaining blood cells using lymphocyte separation medium. Extracted nucleoprotein from mononuclear cells, and measured OD values using ultravioletvisible spectrophotometer at 595 nm. Nuclear protein concentration can be derived by drawing the standard curve. And then by ELISA, determined the concentration of NF-κB. Applied SPSS14.0 statistical software for statistical analysis, and processed the data by using t-test,linear correlation analysis. There was statistically significant(Р<0.05).Results:①NF-κB concentration of peripheral blood mononuclear cells of stable COPD patients was 457.14±227.95, and comparing with the normal control group, NF-κB concentration (87.22±33.41) was significantly higher (Р<0.05).②The stable COPD patients'serum concentration of TNF-α, IL-8, IL-6 and IL-1 were separately 60.41±13.04, 45.23±4.03, 49.01±6.12, 32.41±6.52, and comparing with normal control group were significantly higher, with statistical significance(Р<0.05).③Stable COPD patients'expression of NF-κB positively correlated to serum concentrations of TNF-α, IL-8, IL-6, IL-1, and the correlation coefficients were r = 0.407, r = 0.763, r = 0.485, r = 0.607.④FEV1.0 significantly negatively correlated to concentrations of NF-κB, TNF-α, IL-8 (r =-0.428, r =-0.388, r =-0.538,Р<0.05); TNF-αsignificantly negatively correlated to body mass index (r =-0.433,Р<0.05) , while the IL-6, IL-1 and body mass index had a negative correlation trend, but did not reach statistically significant level; the 6-minute walking distance significantly negatively correlated to NF-κB, IL-8 (r =-0.465, r =-0.418,Р<0.05),and TNF-α, IL-6, IL-1 and body mass index had a negative correlation trend, but did not reach statistically significant level.⑤There was a significant positive correlation between lung function and 6-minute walking distance (r = 0.535,Р<0.05);there was a positive correlation trend between body mass index and lung function, and 6-minute walking distance, but did not reach statistically significant level.Conclusion: NF-κB in the inflammatory response of COPD plays an important role, even in the stable phase it's activity increasing. The continuously activated NF-κB raise target genes transcription activity, including a variety of inflammatory factors genes. The stable COPD patients'serum concentration of TNF-α, IL-8, IL-6 and IL-1 significantly increase, which demonstrats chronic inflammation of COPD not only in the lungs, but also make a systemic inflammatory response, manifested as weight loss, malnutrition, skeletal muscle dysfunction, osteoporosis and so on, which led to the decrease of stamen and reduction of 6-minute walking distance in patients.