Childhood asthma as an allergic disease: rationale for the development of future treatment

The fundamental abnormality in asthma is inflammation of the airways. T-hel per 2 (Th2) lymphocytes are the key orchestrators of this inflammation, ini tiating and propagating inflammation through the release of Th2 cytokines. Interleukins(IL)-4, IL-5 and IL-13. IL-4 and IL-13 promote IgE production b y B-cells, mast cell growth and differentiation, and upregulate adhesion mo lecule expression on vascular endothelium. IL-4 also promotes differentiati on of uncommitted Th0 lymphocytes into Th2 lymphocytes. IL-5 promotes diffe rentiation and recruitment of eosinophils and activates them to degranulate within tissues, resulting in damage to the respiratory epithelium. Current treatment of childhood asthma relies predominantly on corticosteroids that have nonspecific anti-inflammatory activity and are associated with potent ial side-effects. Novel therapies that selectively target the underlying im munopathogenesis hold great promise. Disruption of the Th2 lymphocyte induc ed allergic inflammatory response represents a novel approach to selectivel y inhibiting allergic inflammation at its origin. Possible therapeutic inte rventions include inhibition of Th2 response (CpG oligonucleotides, vaccina tion, CTLA4Ig fusion protein, IL-12, IL-10), inhibition of IgE (the anti-Ig E antibody rhuMAb-E25 omalizumab, which is undergoing clinical trials), inh ibition of mediator activity (leukotriene modifiers. which are approved for use in childhood asthma), and targeting Th2 cytokines (soluble IL-4 recept ors, IL-5 antibody, IL-13). Other therapeutic approaches targeting downstre am events in the allergic inflammatory cascade are also currently under inv estigation (chemokine receptors CCR3, tryptase inhibitors, and inhibitors o f cyclic AMP-specific phosphodiesterase 4). Conclusion: as we further under stand the pathophysiology of asthma, the potential to develop novel treatme nts increases. This paper addresses current possible new treatments for the future.