Cytokine modulators as novel therapies for asthma.

Cytokines play a critical role in orchestrating and perpetuating inflammation in asthmatic airways and several specific cytokine and chemokine inhibitors are now in development for the treatment of asthma. Inhibition of IL-4 with soluble IL-4 receptors has shown promising early results in asthma. Anti-IL-5 antibody is very effective at inhibiting peripheral blood and airway eosinophils but does not appear to be effective in symptomatic asthma. Inhibitory cytokines, such as IL-10, interferons, and IL-12 are less promising because systemic delivery produces intolerable side effects. Inhibition of TNF-alpha may be useful in severe asthma. Many chemokines are involved in the inflammatory response of asthma, and small-molecule inhibitors of chemokine receptors are in development. CCR3 antagonists are now in clinical development for the treatment of asthma. Because so many cytokines are involved in asthma, drugs that inhibit the synthesis of multiple cytokines may prove to be more useful. Several such classes of drug are now in clinical development, and the risk of side effects with these nonspecific inhibitors may be reduced by the inhaled route of delivery.