Immune Prophylactic Effect Of Mycobacterium Vaccae Vaccine On Asthmatic Guinea Pig

Objective: The characteristic features of bronchial asthma include chronic airway inflammation, airway hyperresponsiveness and reversible air flow obstruction, which has a close relation with the imbalance of Thl/Th2 immune response. The abnormal immune response of asthma show the enhanced Th2 immune response(the increased type 2 T-helper cells and hyperfunction) and the suppressed Th1 immune response(the decreased type 1 T-helper cells and hypofunction), so shifting the predominant Th2 immune response towards the predominant Thl immune response by regulating the Th1/Th2 balance is a effective pathway for asthma prevent and treatment. Mycobacterium vaccae vaccine was manifested to be a potent enhancer of Thl immune response, which could suppress the production of Th2 cytokine such as IL-4 and IL-5, improve the production of Thl cytokine such IFN-γ, and induce the immune balance to shift from Th2 response to Thl response. Our objective is to study the immune prophylactic effect of Mycobacterium vaccae vaccine on asthma guinea pig model established by using OVA(ovalbumin).Methods: 30 guinea pigs were divided into NS, Asthma and Mycobacterium vaccae vaccine(M.vaccae) groups at random. Every group had 10 guinea pigs. A guinea pig model of asthma was established with ovalbumin. Every guinea pig of M.vaccae group was injected intramuscularly with 22.5μg M.vaccae 10 days before ovalbumin immunization.For all guinea pigs, pulmonary function[Re(expiratory resistance), FRC (functional residual capacity), FEV03(forced expiratory volume in 0.3 second)] and airway hyperresponsiveness[PC20M (the provocative concentration of inhaled nebulized methacholine causing a 20% increase in Re value by the baseline one caused by inhaling PBS)]were measured using Type AniRes 2000 animal pulmonary function measurement system , total IgE, ovalbumin-specific IgE and ECP (eosinophil cationic protein) in serum were determined using fluorescence enzyme labelling method, inflammation cells in bronchoalveolar lavage fluid were counted, pathological change of lung tissue were observed with light microscopy and electron microscopy, mRNA expression of IL-4, IL-5, IFN-y and Eotaxin in lung tissue were determined with ISH (in situ hybridization) technique, the eosinophil apoptosis in lung was determined with TUNEL(terminal deoxynucleotidyl transferase mediated dUTP nick end labeling) technigue, Fas and Bcl-2 protein expression in lung tissue were determined with IHC(immunohistochemistry) technique after the last challenge.Results:(1) Compared with Asthma model group, M.vaccae group had less mRNA expression(optical density value) of IL-4, IL-5 and Eotaxin (all p<0.05) but more mRNA expression of IFN-y(p<0.05) in lung tissue.(2) Compared with Asthma model group, M.vaccae group had fewer eosinophils, total white cells, and lower percentage of eosinophil to total white cells in BALF(bronchoalveolar lavage fluid)(all /?<0.01).(3) Compared with Asthma model group, M.vaccae group had lower level of total IgE, ovalbumin-specfic IgE and ECP(eosinophil cationic protein) in serum (all/?<0.05).(4) There were a number of inflammation cells in airway( the most of inflammatory cells were eosinophils) and evident inflammation response inlung tissue of Asthma model group, but there were only a few eosinophils in airway and significant slighter inflammation response in lung tissue of M.vaccae group compared with Asthma model group.(5) Compared with Asthma model group, M.vaccae group had lower value of Re and FRC(/?<0.01, p<0.05 respectively), and higher value of FEV0.3(p<0.01).(6) Compared with Asthma model group, M.vaccae group had higher value of PC2om(P