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Departments of
*
Pathology and
Pediatrics, University of Michigan Medical School, and
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109
The development of severe childhood asthma may be influenced by several factors including environmental and infectious stimuli. The causal relationship between infectious viral responses, such as respiratory syncytial virus (RSV), and severe asthma during early childhood is unclear. In these studies, the ability for an initial RSV infection to exacerbate and promote a more severe asthmatic-type response was investigated by combining established murine models of disease. We examined the ability of RSV to induce exacerbation of allergic disease over a relatively long period, leading to development of severe airway responses including airway inflammation and hyperreactivity. The preferential production of IL-13 during a primary RSV infection appears to play a critical role for the exacerbation of cockroach allergen-induced disease. The depletion of IL-13 during RSV infections inhibited the exacerbation and acceleration of severe allergen-induced airway hyperreactivity. This was indicated by decreases in airway hyperreactivity and changes in lung chemokine production. These data suggest that the airway responses during asthma can be greatly affected by a previous RSV infection, even when infection occurs before allergen sensitization. Overall, infection of the airways with RSV can induce an IL-13-dependent change in airway function and promotes an environment that contributes to the development of severe allergic asthmatic responses.
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