Cytokine-directed therapies in asthma

Multiple cytokines play a critical role in orchestrating and perpetuating inflammation in asthma and several specific cytokine and chemokine inhibitors are now in development as future therapy. Anti-interleukin (IL)-5 antibodies markedly reduce peripheral blood and airway eosinophils, but do not appear to be effective in symptomatic asthma. Inhibition of IL-4, despite promising early results in asthma, has been discontinued and blocking IL-13 may be more effective. Inhibitory cytokines, such as IL-10, interferons and IL-12 are less promising, because systemic delivery produces side-effects. Inhibition of tumor necrosis factor (TNF)-α may be useful in severe asthma. Many chemokines are involved in the inflammatory response of asthma and several small molecule inhibitors of chemokine receptors are in development. The CCR3 antagonists (which block eosinophil chemotaxis) are in clinical development for 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 any risk of side-effects with these non-specific inhibitors may be reduced by the inhaled route.