New Approaches for Asthma Modelling

Asthma is a serious global health problem affecting all age groups. Its prevalence is increasing in many countries, especially among children and affecting 1-18% of the population in different countries. There is no effective treatment for this disease. It is necessary to take into consideration the specificity of pathological processes characteristics of different phases of the disease: acute phase, chronic inflammation phase and remission phase for the developing of adequate methods of treatment. And it is also necessary to create an adequate dynamic model that regards the features of all phases of the disease. For the first time the developed model of asthma, which takes into account the pathophysiological processes of the acute phase of the disease and the phase of chronic inflammation, was applied. The design of experiment includes the approaches of systems biology in order to create networks for asthma for different phases of the disease on the basis of the OVA-induced mouse asthma model. The temporal analysis of the target parameters that were selected on the basis of the methods of system biology were studied in 6 groups of animals, 8 in each group, differing in the time of activation of the receptors of innate immunity: before sensitization, after sensitization and at the stage of provocation. Dynamic competition of humoral (IL-1, 4, 5, 6, 13, IgE, IgA, sCD93) and cellular factors (the number of macrophages, neutrophils, eosinophils, lymphocytes in bronchoalveolar lavage) was first investigated during the airway inflammation when the receptors of innate immunity were activated by fragments of bacterial cell walls, simulating the process of natural immunoregulation, carried out by products of decomposition of commensal microflora. Our findings demonstrate the potential of using of a dynamic model on a base of a multifactor analysis of the mechanisms of exposure of fragments of bacterial cell walls, taking into account the dynamics of humoral and cellular factors in different periods of asthma. This approach can be used to investigate the effectiveness of new medicines for the treatment of asthma and makes it possible to clarify the factors that accompany pathological processes, helping to create an adequate strategy for the treatment of the disease.