New anti-asthma therapies: suppression of the effect of interleukin (IL)-4 and IL-5.
Asthma is currently defined as a chronic inflammatory disorder of the airways. The central role of allergen-specific Th2 cells in the regulation of this 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 interleukin (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 secondary antigen exposure, is the possible redundancy with IL-13. Both cytokines share common elements in their receptor and intracellular signalling pathway. 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 allergic inflammation. The importance of IL-5 on eosinophil biology has clearly been established. Conversely, in man, the biological effects of IL-5 are largely limited to eosinophil function. Therefore, IL-5 antagonists offer the unique opportunity of selectively neutralizing the effect of eosinophils. Several strategies have now been developed that successfully inhibit the biological effect of interleukin-4 or interleukin-5. Some of these compounds have proven to be biologically active in man. The challenge now is to establish their therapeutic role in asthma.
Kips
J C
JC
Dept of Respiratory Diseases, Ghent University Hospital, Belgium.
Tournoy
K G
KG
Pauwels
R A
RA
D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000502:physiology; D015848:Interleukin-5 / Q000037:antagonists & inhibitors* / Q000502:physiology
D018927:Anti-Asthmatic Agents; D015848:Interleukin-5; D015847:Interleukin-4