[The role of inflammation in the modulation of bronchial hyperreactivity. Potential therapeutic applications]

The exact functional contribution of the various inflammatory cells, mediators, cytokines and growth factors present in asthmatic airways to bronchial hyperresponsiveness remains to be fully established. Gene knock-out in vivo animal models can provide valuable information in this respect. Obviously, the closer the animal models mimic human disease, the more relevant this information will be. This constitutes the major limitation of murine asthma models to date. Key characteristics of asthma include from a morphological point of view, signs of an acute allergic airway inflammation in combination with airway remodeling, and from a functional point of view, hypersensitivity and hyperreactivity of the airways. Neither of these two main characteristics are properly mimicked in currently developed animal models. The degree of airway hyperresponsiveness obtained in these models is generally small, when compared to the degree of hyperresponsiveness observed in asthmatics. This probably relates at least in part, to the differences in airway inflammation, as in most of the murine models, only acute inflammatory changes are induced without chronic structural changes that might affect responsiveness to a large degree. The shortcomings of these models notwithstanding, gene knock-out models of asthma have revealed some interesting observations. The majority of these models has evaluated the exact functional role of TH2 cells, interleukin-4, interleukin-5 and IgE in the pathogenesis of allergic airway inflammation and airway hyperresponsiveness. Overall, it can be argued that neither the IgE/mast cell axis, nor the IL-5/eosinophil axis, are the cause of airway hyperresponsiveness, but that the T-cell in its own right is the main determining factor in establishing the degree of bronchial hyperresponsiveness.