Individual cytokines contributing to asthma pathophysiology: valid targets for asthma therapy?
Asthma is a common, chronic inflammatory condition of the airways that leads to airway hyperresponsiveness, reversible narrowing of the airways, and airway wall remodeling. Cytokines are involved in various aspects of asthma pathophysiology, such as the polarization of T-helper (Th)2 cells, antigen presentation, immunoglobulin (Ig)E response, airway wall remodeling, and mast cell and eosinophil recruitment and activation. Th2-derived cytokines, such as interleukin (IL)-4, IL-5 and IL-13 contribute to many of these aspects. Inhibition of individual cytokines for asthma therapy has been, and continues to be investigated. Anti-IL-5 monoclonal antibodies did not demonstrate beneficial effects in asthma, with only partial inhibition of eosinophilia in the airway wall; soluble IL-4 receptor, which neutralizes the effects of IL-4, has provided modest improvements in moderate asthma. The anti-IgE monoclonal antibody approach has demonstrated the most benefit in allergic asthma, particularly in severe disease. Which individual cytokine target can be inhibited with beneficial effects comparable to or above that of current inhaled corticosteroids can only be discovered through clinical trials. Blocking the effects of more than one cytokine may be more successful, and greater therapeutic effects may be observed in particular categories of asthma.
Chung
Kian Fan
KF
National Heart & Lung Institute, Imperial College, Dovehouse Street, London, SW3 6LY, UK. f.chung@imperial.ac.uk
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology
D018926:Anti-Allergic Agents; D000911:Antibodies, Monoclonal; D016207:Cytokines