Cytokine-directed therapy in asthma.
Increasing evidence of the pathological roles of multiple cytokines in orchestrating and perpetuating inflammation in asthma has prompted the evaluation of novel anti-cytokine therapies. Anti-IL-5 antibody markedly reduces peripheral blood and airway eosinophils, but does 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 might be more effective. Inhibitory cytokines, such as IL-10, interferons and IL-12 are less promising, as systemic delivery produces side effects. Inhibition of TNF-alpha may be useful in severe asthma. Agents that target IL-13 are still early in the development process. Many chemokines are involved in the inflammatory response of asthma and several small molecule inhibitors of chemokine receptors are in development. CCR3 antagonists, which block eosinophil chemotaxis, are in clinical development for asthma therapy. 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.
Ichinose
Masakazu
M
Third Department of Internal Medicine, Wakayama Medical University, Japan. masakazu@wakayama-med.ac.jp
Barnes
Peter J
PJ
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors*; D006801:Humans; D007378:Interleukins / Q000037:antagonists & inhibitors; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology
D018927:Anti-Asthmatic Agents; D016207:Cytokines; D007378:Interleukins; D019707:Receptors, Chemokine