| The incidence of asthma and other atopic diseases has risen dramatically throughout the past two decades. For genetic natural mutants should be a slow process, the increasing occurrence of atopic diseases is associated with environmental factors to a great extent. As Hygiene Hypothesis proposed, with the enhancing of hygiene and the decreasing of chance to touching pathogenic microorganism and their products, the declining Th1 type of response of the children would be formed which contributed to the atopic diseases developing with dominant Th2 type response. Epidemiological report demonstrated that farming living and contacting cattle can prevent the children from allergies, for frequently touching with the immunogenic organisms and their products would induce the up-regulation of Thl type response and down-regulation of Th2 type response to arrive at immune balance. Based on this hypothesis, we first took the survey of the relations of the concentration of endotoxin in dwelling to allergic asthma in school-age children in china. In addition, exploring the mechanism of endotoxin immunologic regulating the allergic asthma through empirical study. This study should have important significance on analysis and prediction of allergic asthma and give new clue to treatment of such disease.In this epidemiologic investigation, parents of 2986 children at school who were 8 or 12 years of age and living in rural areas of Anqing and Huainan cities were asked to complete a standardized questionnaire including cores questions of International Study of Asthma and Allergies in Childhood, endotoxin content in children's mattress was measured by a kinetic limulus assay, a radioallergosorbent technique-fluorescence enzyme immunoassay(RAST-FEIA) was used to measure the level of specific IgE in serum. Complete data were available for 904 children, the male sight more than the female, there were the negative association between endotoxin level and atopic asthma (OR 0.48, 95% CI 0.32-0.72, P<0.05) and atopic sensitization (OR 0.65, 95% CI 0.49-0.94, P<0.05), but non-atopic asthma and wheeze. It could be concluded that Exposure to endotoxin in early lives of children may have a protective effect on allergic asthma and allergies, which supports Hygiene Hypothesis.Furthermore, in the empirical study for exploring the mechanism of endotoxin immunologic regulating the allergic asthma, 60 mice were divided into four groups: model group using Der f allergen to sensitize and challenge, control group with saline instead of allergen, experimental group A(pro-sensitization LPS + Der f allergen) and experimental group B(post-sensitization LPS + Der f allergen). After isolating the lung of mice and making the pathological section stained by hematoxylin and eosin, the total and differential cells in BALF were counted. Meanwhile, the concentrations of cytokines and specific immunoglobulin were measured by ELISA. Comparing model group, experimental group A had a less total cell and EOS, lower IL-4 and IL-5, a higher IL-12 in BALF(P<0.05), lower sIgE and higher sIgG2a in serum(P<0.05), but experimental group B only had a higher IL-4 in BALF(P<0.05). Another interesting thing was that the IFN-γlevel in experimental group A did not significantly differ from experimental group B and model group. There findings suggest that The exposure to LPS during pro-sensitization can inhibit the infiltration of inflammatory cells and down-modulate the Th2 response of allergic asthma, but that during post-sensitization could not have the function, which further demonstrates that the early exposure to endotoxin could have a protective effect on allergic asthma. However, contrasting with the traditional Hygiene Hypothesis, the early exposure of LPS could not significantly up-regulate the Th1 type of immune responses, which indicates immune tolerance may take a crucial role in immune regulation exerted by LPS. Therefore, these findings should be a necessary complement of Hygiene Hypothesis.
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