Font Size: a A A

Effects Of Bacillus Calmette-Guerin On Airway Inflammation And Blood Thi/Thz Balance In A Mouse Model Of Asthma Department Of Medicine(Respiratory Disease) Medical School Of Zhejiang University

Posted on:2003-06-30Degree:MasterType:Thesis
Country:ChinaCandidate:P L WangFull Text:PDF
GTID:2144360062985485Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Background Asthma is a chronic inflammatory disorders of the airways in which many cells and cellular elements play an important role, associated with variable airflow obstruction ,airway hyperresponsiveness(AHR) and mucus hypersecretion. Many studies suggest that eosinophils (Eos) play a central role in the pathogenesis of asthma, the mechanism of asthma is complex. Increasing evidence suggests mat Th2 lymphocyte play an important role in the mechanism of asthma. They produce Th2 cytokines such as IL-4/ IL-5 initiating and sustaining inflammatory process, and leading to Eos recruitment and activation in the airways. Inversely, Thl lymphocytes secrete different cytokines such as EFN-y and DL-12 inhibiting the production of Th2 cytokines and decreasing allergic response. It has been documented that there is a lower type If type2 cell ratio in asthma so mat there is an attractive idea by regulating the Thl/Th2 balance to reduce allergic response. Bacillus Calmette-Guerin(BCG) is widely used as a prophylaxis of tuberculosis. With the advance of research on the mechanism of BCG, more and more evidences suggest that BCG is a strong inducer of Thl lymphocytes. So we propose that BCG can inhibit the asthma responses inclining to Th2 lymphocytes. Many studies have suggested that BCG promotedIFN-y/IL-l 2 synthesis and inhibited a range of Th2 phenomena including secretion of IL-4/ IL-S, airway eosinophilia and responsiveness to antigens. But it's rare to study the effects of BCG on blood or bone marrow eosinophilia and also there are few reports about the effects of BCG on blood Thl/Th2 balance at the single-cell level.Objective: To investigate the effects of subcutaneous BCG on the airway inflammation blood and bone marrow eosinophilia, airway mucus secretion and the peripheral blood Thl/Th2 balance at the single-cell level.Methods: Male C57BL/6 mice (6-8wk of age, 18-22g of weight) were sensitized and challenged by ovabumin (OVA) as positive group, and mice were treated by saline as negative group. Firstly, we explored an optimal dose and time of BCG infection to suppressing airway eosinophilia, and then the flowing outcomes were analysed after subcutaneous BCG, including bronchoalveolar lavage (BALF), peripheral blood and bone marrow eosinophil numbers, airway mucus secretion, periphral blood Thl/Th2 lymphocytes balance.Results:1. The changes in total and differential numbers of leukocytes of BALF after BCG infection: First we choose BCG 10$CFUs and 2 wk before the first time of OVA challenge as the optimal dose and time of BCG inhibiting airway eosinophilia. We found the total leukocytes and Eos numbers increased significantly in BALF after OVA challenge compared with negative group, (pO.Ol). BCG infection 2wk before OVA challenge resulted in an 85% reduction in Eos numbers of the BALF. But lymphocyte counts in BALF were increased significantly after BCG infection compared with positive group (p<0.05). The other counts including mean total cells, neutrophil and macrophage decreased compared with positive group, but had no statistic difference (p>0.05).2. The changes of total leukocytes and Eos of blood following BCG infection: the blood Eos numbers increased markedly after OVA challenge compared with negative group(p<0.01). But the total leukocytes had no difference. When administration of BCG before OVA challenge the total leukocytes had no change but Eos numbers of blood decreased significantly compared with the positive group (p<0.01), about 70% reduction.3. The changes of total cells and Eos of bone marrow after BCG infection: We found decreased Eos counts (about 50% inhibition) of bone marrow in BCG-infected mice, but the total cells had no difference between the BGC-infected mice and positive group mice.4. The effects of BCG on peripheral blood Thl/Th2 skewing. In negative group mice, CD3+ cells, including CD8+ cells (Tc cells) and CD4+ cells (Th cells), more often expressed IFN-y and less often expressed IL-4, Thl> Th2, Tcl> Tc2. In positive group mice that were immuni...
Keywords/Search Tags:Asthma, Eosinophil, BCG, Th1/Th2, Flow cytometer
PDF Full Text Request
Related items