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The Roles Of Type17Helper Cell And Its Related Cytokines In Airway Inflammation And Remodeling Of Bronchial Asthma

Posted on:2013-01-24Degree:MasterType:Thesis
Country:ChinaCandidate:X AnFull Text:PDF
GTID:2234330395451046Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
BackgroundBronchial asthma is a disease characterized by chronic airway inflammation, participated by a variety of inflammatory cells, such as mast cells, eosinophils and T lymphocytes, where T lymphocytes play a central role. Although the pathogenesis of asthma is not yet fully understood, the current view that Th2cell predominant and the imbalance of Thl/Th2is an important pathogenesis. But in recent years, some experimental and clinical phenomena of asthma can not be completely explained by using theory of Thl/Th2imbalance. Thl7cell is a new subtype of CD4+T cells recently discovered, and may be closely related to asthma. However, what kind of relationship there is between Thl7cells and their associated cytokines expression changes in patients with asthma and asthma is also unknown. So, this problem is urgently worthy of our deep study.ObjectiveWe aim to detect the levels of TGF beta1, IL-17, IL-23of new-onset asthma patients in serum and induced sputum and other airway inflammatory indices, and compare with healthy control group; and we compare their levels before and after three months treatment using inhaled corticosteroids in order to know the significances of TGF beta1, IL-17, IL-23in asthma patients and the changes in airway inflammation. By detecting the serum levels of TGF beta1, IL-17, IL-23in patients with asthma under standardized treatment and other airway inflammatory indices, and comparing their differences in asthma patients with different degrees of obstruction of pulmonary functions, we want to explore the significant roles of TGF beta1, IL-17, IL-23in asthma patients’ airway remodeling. Methods1Use case-control method, we collect25new onset asthma patients as experimental groups and at the same period, select27cases of healthy people as control groups. Record the general information of two groups and collect their serums. Monitor the two groups’ serum expression levels of TGF betal, IL-17, IL-23and compare differences between the two groups in various indicators, including age, sex, serum expression levels of TGF beta1, IL-23, IL-17.2Use self-control method, treat these patients with inhaled corticosteroids for three months, and monitor ACT scores, pulmonary functions, FENO levels, blood regular tests, total IgE of serum, the expression levels of TGF beta1, IL-23and IL-17in serum and induced sputum supernatant. And compare differences of these indicators before and after treatment.3Use case-control method, collect91cases of asthma patients with at least three months’standardized treatment. Using FEV1%as grouping criterion, divide them into three groups:the mild asthma group (FEV1%>=80%) with27patients, the moderate asthma group (60%<FEV1%<80%) with33patients and the severe asthma group (FEV1%<=60%) with31patients. Select27cases of healthy people as control group. Monitor and compare the serum levels of TGF betal, IL-17, IL-23and other inflammatory indices in each group, and explore their relationships with airway remodeling.Results1. Compare to healthy control group, the serum levels of TGF beta1of new onset asthma patients were higher than that in control group (1919.50±221.02pg/ml vs1450.41±366.54pg/ml, p=0.000). There were no significant differences in serum expression levels of IL-17and IL-23between the two groups (4.57±1.05pg/ml vs4.57±0.80pg/ml, p=0.996;188.47±51.57pg/ml vs213.45±32.45pg/ml, p=0.877); and levels of IgE were higher than that in control group (284.81±231.12ng/ml vs30.87±29.07ng/ml, p=0.001)。2. Compare indices before and after treatment, the results show that after treatment serum levels of TGF betal were lower than that before treatment (1292.63±191.23pg/ml vs1919.50±221.02pg/ml, p=0.000). There were no statistically significances in serum levels of IL-17, IL-23and levels of TGF beta1, IL-17, IL-23in sputum supernatant. ACT score after treatment was higher than that before treatment (22.16±4.53points vs14.96±4.25points, p=0.000); FEV1%after treatment was higher than that before treatment (83.4%±15,74%vs72.45%±7.48%, p=0.002); FENO after treatment was lower than that before treatment (49.98±25.98ppb vs109.18±65.23ppb, p=0.000); after treatment, blood cell counts in Eos%droped apparently (4.33%±1.89%vs5.7%+1.85%, p=0.004); Eos%in induced sputum had declined (6.58%±3.66%vs10.0%±4.75%, p=0.004). Before and after treatment, serum IL-17was not linearly correlated with the serum IL-23either was the serum TGF-beta1. FENO was correlated negatively with ACT score (r=-0.425, P=0.034), and correlated positively with FEV1%(r=0.657, p=0.020).3. Compare to healthy people, the serum levels of TGF beta1of standardized treated asthma patients were higher than that in healthy group (2168.50±377.03pg/ml vs1450.41±366.54pg/ml, p=0.000); levels of IL-17of the former were lower than the latter (3.78±0.93pg/ml vs4.57±0.80pg/ml, p=0.000); there were significant differences of IL-23in the two groups (198.57±50.50pg/ml vs213.45±32.65pg/ml, p=0.080).4. Compare eath asthma group, there was significant differences in serum levels of TGF betal and IL-17between mild asthma group and moderate-to-severe asthma group (p<0.05), and no significance between moderate group and severe group. There was no significant difference between each group in FENO levels and serum levels of IL-23. Serum IL-17was correlated negatively with TGF beta1(r=-0.306, p=0.004); and there were no correlation between TGF betal,IL-17and IL-23(r=-0.151, p=0.154; r=0.164, p=0.121). FEV1%was correlated negatively with serum TGF-beta1(r=-0.472, p=0.001), and correlated positively with FEV1%(r=0.448, p=0.000); but not linearly correlated with FEV1%. There were no correlations between FENO and serum IL-17, TGF beta1, FEV1%; and it was correlated negatively with serum IL-23(r=-0.271,p=0.026).Conclusions1. The levels of TGF beta] in new-onset asthma were significantly higher than that in control group, and after treatment with ICS, it was lower than that before treatment. In patients with asthma under standardized treatment, pulmonary functions of moderate and severe asthma were worse than that of mild group, and their serum TGF beta1were negatively correlated with FEV1%, which indicate that TGF beta1is an important index for airway inflammation and remodeling.2Compare the serum levels of IL-17in new-onset asthma with the control group, and their levels before and after ICS treatment, there were no significances. However, in patients with asthma under standardized treatment, the serum levels of IL-17were lower than that in control group. What’s more, pulmonary functions of moderate and severe asthma were much worse than mild group. These demonstrate that IL-17is a complicate cytokine, and may play a dual role in asthma; persistent airway inflammation inhibits its secretion and expression, and then in phase with severe impairment of pulmonary function and severe airway remodeling, its expression declines.3The cytokines associated with Th17cell are a perplexing network, and affected by various factors and influences each other, so we speculate that Th17cells play more and more complicated roles in the pathogenesis of asthma.4FENO is a noninvasive and important indicator for monitoring airway inflammation in asthma. The levels of FENO in patients after ICS treatment are significantly decreased when compared with that of before treatment, and what’s more, they are positively correlated with the scores of ACT. But the levels of FENO are not correlated with FEV1%.
Keywords/Search Tags:TGF beta1, IL-17, IL-23, asthma, inflammation, remodeling
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