Dissertation
Dissertation > Medicine, health > Pediatrics > Children within the science > Department of pediatric respiratory and chest diseases

The Effects of CysLTs、IL-10、TNF-α on Bronchiolitis in Children

Author NanXuanHua
Tutor ChengHuanJi
School Jilin University
Course Pediatrics
Keywords CysLTs IL-10 TNF-α Bronchiolitis children
CLC R725.6
Type Master's thesis
Year 2009
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Background:Bronchiolitis is a common disease in infants below the age of two,and it is caused by a virus infection in acute lower respiratory tract inflammation due to obstructive airway disease, including respiratory syncytial virus is the most common virus.But the virus doctrine still can not fully explain bronchiolitis pathogenesy, such as incidence of the main symptoms are wheezing, dyspnea, the majority of children with elevated serum IgE, some children with wheezing repeatedly after recurrent, 30%-40% of patients maybe develop asthma ,an army of experimental evidences also show that bronchiolitis has the similar mechanism with asthma.At present, the pathogenesy of bronchiolitis has not yet been fully clarified, involved the direct effect of virus, neurological pathological mechanisms and immune pathogenesis and it was clear that cytokines involved in the immune response, inflammation and immune injury, the study of bronchiolitis focused on cytokines and its clinical application by scholars at home and abroad.There is few report the effect of CysLTs, TNF-α, IL-10 in the pathogenesis of bronchiolitis, so it is necessary to deep research.Leukotrienes as an important inflammatory mediators in bronchial asthma, has been unanimously endorsed by scholars at home and abroad, but its effect in bronchiolitis pathogenesis was relatively few reported ,to study the effect of leukotrienes in the pathogenesis of bronchiolitis,it will identify further the dependablity between the bronchiolitis and the bronchial asthma . Leukotrienes is metabolites produced in metabolic pathway that is arachidonic acid through the 5 -lipoxygenase pathway. CysLTs is released by eosinophils, mast cells, macrophages, monocytes and other inflammatory cells ,promotes inflammatory cells at the same time, in particular, EOS gatheres in the airway, causing airway smooth muscle contraction, it can also increased mucus secretion, vascular permeability, and increased airway hyperresponsiveness through promoting airway smooth muscle(ASM) proliferation, growth and promotion of extracellular matrix (ECM) synthesis that would cause airway remodeling. LTs is the intracellular signaling molecule which caused a series of reaction, is a powerful inflammatory mediator, plays an important role in the lung, with a wide range of physiological and pathological effects, may play an important role in the pathogenesis of bronchiolitis.IL-10 is a Th2 type cytokines, which is not only with immunosuppressive or anti-inflammatory effect, but also is the cytokine with a wide range of immunological effects. In the immune response,IL-10 can protect the body side, but it also has the bad side to the body. IL-10 can inhibit the proliferation of Th1 cell and active the Th2 cells,In the balance of Th1/Th2,it can promote the Th0 cells turn to Th2 cells,so it is the anti-inflammatory cytokines which againsts airway inflammation reaction .Some studies shown that the little secretion of IL-10 would lead to variety inflammatory processes,and its lack of secretion will lead to sustained inflammation and irreversible tissue damage in some cases. Immune response is the complex and precise immune regulation network which is constituted by the control factors, as an important immunoregulatory factor, IL-10 may play a role in the pathogenesis of Bronchiolitis,and its positive and negative effects is worth to further studying.Tumor necrosis factor is a protein produced by monocyte-macrophage system,which is not only an effective antitumor factor,but also is an important regulatory factor of body inflammation and immune response. Under normal circumstances,an appropriate amount of TNF-αin plasma have the effects of immune regulation,physiological functions of the body and antiinfective, antitumor effects and so on, on the other hand,if the sustained release of TNF-α,it may cause excessive heat,shock and cachexia etc. At the same time, IL-6, IL-8,IL-10 and other cytokines can be further induced by TNF-α,these pro-inflammatory cytokines involved in acute response of the body,fever response,the release of chemotactic peptide and so on.which can also increase the cells vascular permeability by activeing endothelial cells and other adverse reactions. TNF-a is widely distributed in the each airway and involved in the process of chronic inflammation of the airway,so it is likely to play a role in pathogenesis of Bronchiolitis.Objective: Investigate the effect of the cytokine CysLTs, IL-10 and TNF-αin the pathogenesy of bronchiolitis, and analysis the dependability betweet the levels of cytokines in the acute phase and the more recurrent wheezing after rec- over from the bronchiolitis .Methods: serum CysLTs, IL-10 and TNF -αlevel are measured in 30 cases of children with of the acute phase of bronchiolitis, 16 cases of children with bronchiolitis of the recovery phase and 20 cases of healthy children,by doubleantibody sandwich enzymelinked immunosorbent assay (ELISA) respectively, and 6 months follow-up the frequency of the wheezing after the recover of bronchiolitis. Application of statistical analysis SPSS12.0. Results(1).Compared the levels of serum CysLTs, IL-10 and TNF-αin the acute ph- ase of bronchiolitis , recovery phase of bronchiolitis and the healthy control grou- p:①The level of serum CysLTs in patients with bronchiolitis of the acute phase was higher than recovery phase (363.57±51.33 VS 305.67±37.96pg/ml), with statistical significance; The level of serum CysLTs in patients with bronchiolitis of the acute phase was higher than healthy control group (363.57±51.33 VS 114.37±35.89pg/ml), with statistical significance; The level of serum CysLTs in patients with bronchiolitis of the recovery phase was higher than healthy control group(305.67±37.96VS114.37±35.89pg/ml),with statistical significance;②The level of serum IL-10 in patients with bronchiolitis of the acute phase was lower than the recovery phase (7.79±2.14 VS 10.99±1.99pg/ml),with statistical significance; The level of serum IL-10 in patients with bronchiolitis of the acute phase was lower than the healthy control group(7.79±2.14 VS 18.84±2.69pg/ml), with statistical significance; The level of serum IL-10 in patients with bronchiolitis of the recovery phase was still lower than the healthy control group(10.99±1.99 VS 18.84±2.69 pg/ml), with statistical significance.③The level of serum TNF-αin patients with bronchiolitis of the acute phase was higher than the recovery phase(59.72±18.77 VS 46.46±12.80 pg/ml),with statistical significance; The level of serum TNF-αin patients with bronchiolitis of the acute phase was higher than that of healthy control group (59.72±18.77 VS 40.24±12.20pg/ml), with statistical significance; There was no statistically difference between the levels of serum TNF-αin patients with bronchiolitis of the recovery phase and the healthy control group(46.46±12.80 VS 40.24±12.20pg/ml).2. As the patients with bronchiolitis of the acute phase were cured, they were retrospectively analyzed after 6 months follow-up: Dividing groups in accordance with the times of recurrent wheezing , wheezing attack was not less than 2 times for group A, breathing attack was not more than 1 times for group B.①The level of serum CysLTs in patients with bronchiolitis of the acute phase in group A was higher than group B(416.48±48.35 VS 324.20±41.08pg/ml), with statistical significance; The level of serum CysLTs in patients with bronchiolitis of the acute phase in group A was higher than the healthy control group (416.48±48.35 VS 114.37±35.89pg/ml), with statistical significance; The level of serum CysLTs in patients with bronchiolitis of the acute phase in group B was higher than the healthy control group (324.20±41.08 VS 114.37±35.89pg/ml), with statistical significance.②The level of serum IL-10 in group A was lower than group B in acute phase(6.38±2.03 VS 8.51±1.80pg/ml), with statistical significance; The level of serum IL-10 in patients with bronchiolitis of the acute phase in group A was lower than the healthy control group (6.38±2.03 VS 18.84±2.69pg/ml), with statistical significance; The level of serum IL-10 in patients with bronchiolitis of the acute phase in group B was lower than the healthy control group (8.51±1.80 VS 18.84±2.69pg/ml), with statistical significance.③The level of serum TNF-αin group A was higher than group B in acute phase(73.18±12.70 VS 46.02±7.29pg/ml), with statistical significance; The level of serum TNF-αin patients with bronchiolitis of the acute phase in group A was higher than the healthy control group (73.18±12.70 VS 40.24±12.20pg/ml), with statistical significance; There was no statistically difference between the level of serum TNF-αin patients with bronchiolitis of the acute phase in group B and the healthy control group(46.02±7.29 VS 40.24±12.20pg/ml).Conclusion: The acute phase of bronchiolitis CysLTs serum levels was higher than those in healthy control group, recovery phase was lower than the acute stage, but still higher than the healthy control group, suggesting that CysLTs may be involved in the pathogenesis of bronchiolitis. Bronchiolitis acute phase serum levels of IL-10 was lower than the healthy control group, and the state of recovery remained low, suggesting that IL-10 may be involved in the pathogenesis of bronchiolitis. Acute phase of bronchiolitis serum TNF-αlevels was higher than the recovery group, recovery group and the healthy control group had no significant difference, suggesting that TNF-αmay be involved in the pathogenesis of bronchiolitis. While the levels of serum CysLTs, TNF-αis higher in acute phase of bronchiolitis,the level of IL-10 is lower, there is more likelihood wheezing again after the attack. Dynamic monitoring of serum levels of cytokines, could be observed effect of bronchiolitis clinical observation, treatment direction, the prognosis of patients etc,as a reference indicator.

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