| Background Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play an important role, associated with mucus hypersecretion, variable airflow obstruction and airway hyperresponsiveness(AHR). The mechanism of asthma is complex, but it has been documented that there is a lower Th1/ Th2 cell ratio in asthma, which is biased toward the Th2 type and defective in the Th1 type. In contrast, more evidences suggest that BCG is a strong inducer of Th1 lymphocytes, which promote IFN-γ, IL-12 synthesis and inhibit airway eosinophilia and AHR in mouse model of asthma as in asthma patients. The occurrence of atopic diseases have been increasing in developed countries, the reasons are largely unkown. In 1997, Shirakawa T et al. found the inverse association between the tuberculin response and atopic disorders in Japanese children. William O and other authors also confirmed the increased prevalence of asthma was associated with the declining infection with agents such as Mycobacterium tuberculosis, measles, so "hygiene hypothesis" has been provided. It is an attractive idea whether early vaccination with BCG can prevent the occurrence of asthma later? Few studies show newborns developed a th|-type immune response, and inhibited the allergic inflammation and AHR, but there is no reports about the preventive effectsof BCG vaccinated early with lower dose(such as 103 CFU) on airway inflammation and mucus production in mouse models of asthma.. Objective: Based on a mouse model of asthma we created previously, newborn C57BL/6 mice were vaccinated subcutaneously with BCG early, later sensitized and challenged, then we examine the effects on the airway inflammation and the lung Th1/Th2 cytokines mRNA balance, as well as whether the preventive effect of low-dose BCG is compatable to that of large-dose BCG.Methods: Newborn C57BL/6 mice (in 24 hours after birth,n=33 ) were assigned to five groups: normal saline solution group(A group,n=7), asthma model group(group B,n=7), low-dose(103 CFU) BCG-vaccinated group ( group C , n=7 ) ,moderate-dose(104 CFU) BCG-vaccinated group ( group D , n=5) ,high-dose(l05CFU) BCG-vaccinated group (group E, n=7) , subcutaneously injected BCG four times at 0 week, 1 st week, 2nd week and 3rd week respectively; While group A and B injected by saline solution. After 6th week, group E were sensitized and challenged by saline solution, other groups by ovabumin(OVA). After the last challenge, the mice were sacricfied, then the bronchoalveolar lavage (BALF) inflammatory cells were counted, and the pathomorphological changes in the lung analyzed. The expressions of Th1 cytokine (IFN) mRNA and Th2 cytokine (IL-4) mRNA were measured by reverse trancription-polymerase chain reaction( RT-PCR).Results:1. The effects of BCG vaccination on airway inflammation1. The changes of the number of the total cells and EOS in BALF The total white blood cells in BALF were significantly increased in group B and BCG-vaccinated groups(P < 0.01, P < 0.05) compared with group A ; But compared with group B, no significant differences in different-dose BCG-vaccinated groups(P>0.05); While EOS in BALF were significantly increased (P<0.01, P<0.05) in all other groups compared with group A, but compared with group B, which was significantly decreased(P<0.01, P<0.05) in all BCG-vaccinated groups1.2 The changes of pulmonary pathology on airway inflammationIn group A, there are no EOS accumulation around airways and vessels, inverselythere are large amount of inflammatory cells and EOS around airways and vessels ofgroup B, while in all BCG-vaccinated groups , there are still a lot of inflammatorycells, but EOS infiltration in the alveolar wall decreased significantly compared withgroup B.2.The effects of BCG vaccination on the balance of Th|/Th2 cytokines mRNACompared with group A, the expression of IFN mRNA was lower in group B andhigh in all BCG-vaccinated groups, though ther... |
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