New anti-asthma therapies: suppression of the effect of interleukin (IL)-4and IL-5

Asthma is currently defined as a chronic inflammatory disorder of the airwa ys. The central role of allergen-specific Th2 cells in the regulation of th is mucosal airway inflammation has been highlighted. Hence, there is large interest in the therapeutic potential of an anti-Th2 cell approach. One of the strategies which has been developed, is to inhibit the effect of interl eukin (IL)-4 or IL-5, two main Th2 cell derived cytokines. Interleukin-4 is pivotal in the pathogenesis of allergic disorders through its wide range of effects. An important observation, especially during seco ndary antigen exposure, is the possible redundancy, with IL-13. Both cytoki nes share common elements in their receptor and intracellular signalling pa thway. As a result, compounds can be developed that selectively inhibit the effect of either IL-4 or IL-13, or alternatively, by interfering with the common pathway, inhibit the effect of both cytokines. Eosinophils are generally seen as a particularly harmful element in the all ergic inflammation. The importance of IL-5 on eosinophil biology has clearl y been established. Conversely, in man, the biological effects of IL-5 are largely limited to eosinophil function. Therefore, IL-5 antagonists offer t he unique opportunity of selectively neutralizing the effect of eosinophils . Several strategies have now been developed that successfully inhibit the bi ological effect of interleukin-1 or interleukin-5. Some of these compounds have proven to be biologically active in man. The challenge now is to estab lish their therapeutic role in asthma.