| Background: The prevalence rates of asthma and other atopic disorders have increased steadily over the past few decades. The underlying mechanisms for this phenomenon remain largely unknown. Since the natural mutation rate is low, altered environmental and life style conditions are thought to play an important role. High exposure to house dust mite allergens has been shown to predispose to allergic sensitization and to the development and persistence of asthma. Epidemiological and clinical studies have provided evidences that infections may prevent the development of atopy and atopic disease. Recent investigations have demonstrated that Bacille Calmette-Guerin (BCG), a potent inducer of TH1 response, infection prior to allergen sensitization inhibits TH2 immune response to the allergen. The prenatal period and early childhood are considered to be critical for the establishment and maintenance of a normal TH1/TH2 balance. Immune modulation at this stage may be a way forward in the prevention of allergy. Objective: We want to investigate the effect of maternal differentkinds of antigen exposure during pregnancy and neonatal exposure in the early life on the development of asthma and whether a preexisting TH1 type immune response elicited by BCG immunization could suppress allergic sensitization in an animal model. Methods: 1. Rats were sensitized by intraperitoneal and subcutaneous injections of ovalbumin (OVA) and AI(OH)3 twice, then received 6 consecutive airway allergen challenges by aerosolization. The plasma samples were obtained to determine the OVA-specific IgE antibody titers. The peripheral blood mononuclear cell (PBMC) was cultured to measure the cytokine production. Bronchoalveolar lavage and differential cell counts of BAL fluid were performed. At last, the lung tissue was prepared for analysis the pathology change of asthma. The expression of IL-4 mRNA was determined by in situ hybridization.2. Rats were divided into five groups according to the different treatment, M- N-,M BCG+ N BCG+,M Der p+ N Der p+,M BCG+ N BCG- and M Der p+ N Der p- (M=mater, N=neonate,- means the rats were treated with NS instead of BCG or Der p). A pretreatment of 5×104 colony forming units of BCG was done at the 12th day of pregnancy and the first 36-48 hours of the neonatal rat. A presensitization of 5000SBE Der p was done at the 11th, 18th days of pregnancy and the first 2,9,16 days of the neonatal rat. All rats were sensitized and provoked with OVA to establish the animal model of asthma when they were 30-day old,followed by collection of the BALF, the lung tissue, the plasma samples, the supernatants of PBMC and their relevant indexes measurement. Results:1. Compared with the control group, the plasma OVA-specific IgE level of the model group was significantly increased; IL-4 production significantly increased and IFN-( decreased resulting in a markedly increased ratio of IL-4/ IFN-( in PBMC supernatant of model group; eosinophil counts in BALF were also increased; the allergic airway inflammation was indicated by a marked eosinophil and other inflammatory cells influx into the lungs.2. In the group which mater and infant are both exposed to Der p (M Der p+N Der p+), IL-4 level was significantly higher and IFN-γlevel was lower than those in the control group (M-N-), resulting in a markedly increased ratio of IL-4/IFN-γ, which indicated a TH2 profile. As to the M Der p+N Der p- group, there were no significant differences compared with the control. The TH2 dominance of M Der p+N Der p+ group was more obvious than that of M Der p+ N Der p- group.3. In comparison with the control, BCG immunization could increase the production of IFN-γ,reduce IL-4, IL-4/IFN-γratio and plasma OVA-specific IgE level significantly in the group M BCG+N BCG+. There also showed a significant TH1 dominance in the PBMC cytokine production even if the infants were not inoculated with BCG in their first day (M BCG+N BCG-). No significant difference in plasmaOVA-specific IgE level existed...
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