Mlk. Tang et Cve. Powell, Childhood asthma as an allergic disease: rationale for the development of future treatment, EUR J PED, 160(12), 2001, pp. 696-704
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.