chapter  17
28 Pages

Cytokine Regulation of Bronchial Hyperresponsiveness

How exactly each of the cytokines present in asthmatic airways regulates BHR also is unclear. Compared with normal individuals, asthmatic airways contain increased amounts of a multitude of cytokines, which can grossly be grouped into T-helper 2 (Th2), proin£ammatory, and ¢brogenic cytokines, as well as chemokines. In addition, reduced levels of immumodulatory molecules, such as interleukin-12 (IL-12) or interferon-g (IFN-g), have been reported (8) (Fig. 2). At present, the potential contribution of these various groups is deduced from descriptive data in humans, coupled to a more functional analysis in in vivo animal models. An obvious limitation of this approach has been the lack of an animal model that fully re£ects all features of asthma. Most of these models display a short-lived, relatively small increase in airway responsiveness. In addition, the morphological alterations are usually limited to acute in£ammatory changes. However, attempts are now increasingly undertaken to develop in vivo animal models that display features of airway remodeling and a more persistent increase in airway responsiveness, thus mimicking more closely human asthma (9). Together with the increased availability of speci¢c cytokine antagonists for human use, it can be anticipated that this will lead to better insight into the cytokine regulation of BHR. This, in turn, will probably result in novel therapeutic strategies.