The Study Of Relationship Between The Serum And Induced Sputum Th17Cells Associated Factors And BODE Index In Stable COPD

【Background】Chronic obstructive pulmonary disease (COPD) is a preventable and treatablecommon diseases characterized by persistent airflow limitation.Showed progressivedevelopment of airflow limitation, the increase in chronic inflammatory reactions isdue to airway and lungs with noxious particles or gases. Patients with acuteexacerbations and complications affect the overall severity. So far the pathogenesis ofCOPD is not yet fully understood. Chronic airway inflammation in COPD as one ofthe important pathogenesis, COPD is generally considered more airways, lungparenchyma, and pulmonary vascular chronic inflammation characterized mainlyneutrophil accumulation in the lumen, T lymphoid cells and macrophage infiltrationin the wall, activated inflammatory cells release a variety of inflammatory mediators,resulting in pulmonary protease/antiprotease imbalance, oxidant/antioxidantimbalance, apoptosis/anti-apoptotic imbalances, so as to promote a variety ofinflammatory cells in lung inflammation and destruction of the structure, resulting inairway stenosis, emphysema formation and increased resistance to airflow. In recentyears, many foreign studies have found that the presence of a novel cell is differentfrom the Th1and Th2CD4+effector T cells, helper17cells (Th17). In the case ofTGF-β1and IL-6(starts factors) exist, Naive T cells differentiate into Th17cellsdirection. The cells not only have separate regulatory mechanisms of differentiationand development, but also produce IL-17, IL-21, IL-6and other effectors specifically.The process of surviving and maintaining the functional activity of the Th17cells ismediated by IL-23. IL-17binding to the relevant receptor activation by MAP kinase pathway and NF-kB plays important biological activities. Promoting theinflammatory response is a major biological function of IL-17, and autoimmuneosteoarthritis, rheumatoid arthritis, multiple sclerosis, psoriasis, and transplantrejection, asthma, COPD and so has very close ties. Currently simple pulmonaryfunction test has been unable to meet the medical assessment of the COPD patient’scondition, BODE index as a new assessment of the patient’s condition and prognosisof COPD multidimensional grading system, is a reliable assessment parameters aboutmorbidity and mortality in patients with COPD. Including four indicators: body massindex, degree of airflow obstruction, dyspnea, and exercise capacity. Based on BODEindex criteria, calculate the final BODE index score. The higher BODE index scoreis, the more serious illness, the worse treatment and prognosis.Current less researchrelated factors of Th17cells in patients with stable COPD to airway and systemicinflammation changes and in quality of life and prognosis assessment, so exploringthese cytokines on disease assessment and treatment of patients with COPD isimportant.【Objective】To investigate the serum and induced sputum cytokines associated with Th17cells in patients with stable chronic obstructive disease interleukin17(IL-17),interleukin12(IL-12p70), interleukin6(IL-6) and transforming growth factor β1(TGF-β1) changing levels and explore the relevance of these four cytokines betweenBODE index and provides new methods for the assessment of the condition andprognosis in patients with COPD.【Method】Stable COPD patients in our hospital confirmed by pulmonary function test30cases, including18males and12females; selected the normal pulmonary function inhealthy control group of30patients, including16males and14females.All subjectsperformed pulmonary function tests, height, weight detection, dyspnea score,6-minute walk distance was measured, serum and induced sputum specimens IL-17,IL-12p70, IL-6, TGF-β1levels are tested. 【Results】(1) In generalStable COPD group of30patients,18males and12females,(60.97±9.84) yearsold; normal control group of30patients,16males and14females,(55.87±12.39)years of age. There was no significant difference between both groups of gender andage.(2) Levels of serum IL-17, IL-12p70, IL-6, TGF-β1measured resultsLevels of serum IL-17in stable COPD patients and healthy control group were(1.27±0.69) pg/ml,(0.74±0.73) pg/ml; the difference was statistically significant(t=2.848, P=0.006). Levels of serum IL-12p70in stable COPD patients and healthycontrol group were (0.88±0.47) pg/ml,(0.50±0.38) pg/ml; the difference wasstatistically significant (t=3.436, P=0.001). Levels of serum IL-6in stable COPDpatients and healthy control group were (8.22±6.23) pg/ml,(3.49±2.06) pg/ml;the difference was statistically significant (t=3.956, P=0.000). Levels of serumTGF-β1in stable COPD patients and healthy control group were (79.67±41.41) pg/ml,(33.05±17.28) pg/ml; the difference was statistically significant (t=5.692, P=0.000).(3) Levels of induced sputum IL-17, IL-12p70, IL-6, TGF-β1measured resultsLevels of induced sputum IL-17in stable COPD patients and healthy controlgroups were (9.38±3.39) pg/ml,(4.83±2.22) pg/ml; the difference wasstatistically significant (t=6.146, P=0.000). Levels of induced sputum IL-12p70instable COPD patients and healthy control groups were(4.95±2.11) pg/ml,(1.98±1.70) pg/ml; the difference was statistically significant (t=6.027, P=0.000). Levelsof induced sputum IL-6levels in stable COPD patients and healthy control groupswere (411.13±290.24) pg/ml,(125.97±56.82) pg/ml; the difference wasstatistically significant (t=5.281, P=0.000). Levels of induced sputum TGF-β1instable COPD patients and healthy control groups were (206.48±121.06) pg/ml,(48.80±20.66) pg/ml; the difference was statistically significant (t=7.032, P=0.000).(4) The measurement results of BODE index BMI in stable COPD patients and healthy control group were (21.65±3.95)kg/m2,(23.49±2.68) kg/m2, the difference was statistically significant (t=-2.113, P=0.040). FEV1%of two groups were (48.89±20.42)%,(102.98±12.16)%, thedifference was statistically significant (t=-12.469, P=0.000). mMRC scores of twogroups were (1.60±0.97),1[(0~1)], the difference was statistically significant(Z=-3.367, P=0.001).6MWD of two groups were (396.13±80.20) m,(451.27±70.00) m, the difference was statistically significant (t=-2.837, P=0.006). BODEindex score of the two groups of subjects were (3.07±2.35),0[(0~0.25)], there was asignificant difference (Z=-5.241, P=0.000).(5) Relationship between stable COPD group IL-17, IL-12p70, IL-6, TGF-β1and BODE index and various components.Serum IL-17, IL-12p70, IL-6, TGF-β1levels correlated with BODE index (r andP values were: r=0.885, P=0.000, positive correlation; r=0.846, P=0.000,positive correlation; r=0.824, P=0.000, positive correlation; r=0.894, P=0.000,positive correlation). Induced sputum IL-17, IL-12p70, IL-6, TGF-β1levelscorrelated with BODE index (r and P values were: r=0.661, P=0.000, positivecorrelation; r=0.840, P=0.000, positive correlation; r=0.940, P=0.000, positivecorrelation; r=0.964, P=0.000, positive correlation).Serum IL-17, IL-12p70, IL-6, TGF-β1levels correlated with BMI (r and Pvalues were: r=-0.604, P=0.000, negative correlation; r=-0.530, P=0.003,negative correlation; r=-0.447, P=0.013, negative correlation; r=-0.534, P=0.002,negative correlation). Induced sputum IL-17, IL-12p70, IL-6, TGF-β1levelscorrelated with BMI (r and P values were: r=-0.301, P=0.106, no correlation; r=-0.497, P=0.005, negative correlation; r=-0.422, P=0.020, negative correlation; r=-0.458, P=0.011, negative correlation).Serum IL-17, IL-12p70, IL-6, TGF-β1levels correlated with FEV1%(r and Pvalues were: r=-0.831, P=0.000, negative correlation; r=-0.788, P=0.000,negative correlation; r=-0.687, P=0.000, negative correlation; r=-0.832, P=0.000,negative correlation). Induced sputum IL-17, IL-12p70, IL-6, TGF-β1levelscorrelated with FEV1%(coefficient r and P values were: r=-0.615, P=0.000, negative correlation; r=-0.799, P=0.000, negative correlation; r=-0.788, P=0.000, negative correlation; r=-0.856, P=0.000, negative correlation).Serum IL-17, IL-12p70, IL-6, TGF-β1levels and6MWD correlation (r and Pvalues were: r=-0.492, P=0.006, negative correlation; r=-0.467, P=0.009,negative correlation; r=-0.597, P=0.000, negative correlation; r=-0.631, P=0.000, negative correlation). Induced sputum IL-17, IL-12p70, IL-6, TGF-β1levelscorrelated with6MWD (r and P values were: r=-0.550, P=0.002, negativecorrelation; r=-0.399, P=0.029, negative correlation; r=-0.682, P=0.000,negative correlation; r=-0.702, P=0.000, negative correlation).Serum IL-17, IL-12p70, IL-6, TGF-β1levels and mMRC score correlation (r andP values were: r=0.561, P=0.001, positive correlation; r=0.504, P=0.005,positive correlation; r=0.553, P=0.002, positive correlation; r=0.506, P=0.004,positive correlation). Induced sputum IL-17, IL-12p70, IL-6, TGF-β1levels andmMRC score correlation (r and P values were: r=0.682, P=0.000, positivecorrelation; r=0.503, P=0.005, positive correlation; r=0.649, P=0000, positivecorrelation; r=0.643, P=0000, positive correlation).【Conclusion】1. The levels of stable COPD group serum and induced sputum IL-17, IL-12p70,IL-6, TGF-β1were higher than the healthy control group, all involved in thepathogenesis of COPD exacerbations with gradually increased, closely related to theseverity of COPD.2. Stable COPD group BODE index score was higher than the healthy controlgroup, and with serum and induced sputum IL-17, IL-12p70, IL-6, TGF-β1correlated,lung function, body mass index, dyspnea score and6minutes walking distance canassess the severity of COPD disease，can be common for the diagnosis and treatmentguidelines for COPD, but also for the prognosis of high clinical value.