title: Targeting the interleukin pathway in the treatment of asthma.
abstract: Asthma is a common heterogeneous disease with a complex pathophysiology. Current therapies based on inhaled corticosteroids and longacting β2 agonists are effective in controlling asthma in most, but not all patients, with a few patients falling into the severe asthma category. Severe asthma is characterised by poor asthma control, recurrent exacerbations, and chronic airflow obstruction despite adequate and, in many cases, high-dose treatments. There is strong evidence supporting the role for interleukins derived from T-helper-2 (Th2) cells and innate lymphoid cells, such as interleukins 4, 5, and 13, as underlying the eosinophilic and allergic inflammatory processes in nearly half of these patients. An anti-IgE antibody, omalizumab, which binds to circulating IgE, a product of B cells from the actions of interleukin 4 and interleukin 13, is used as treatment for severe allergic asthma. Studies examining cytokine blockers such as anti-interleukin-5, anti-interleukin-4Rα, and anti-interleukin-13 monoclonal antibodies in patients with severe asthma with recurrent exacerbations and high blood eosinophil counts despite use of inhaled corticosteroids have reported improved outcomes in terms of exacerbations, asthma control, and forced expiratory volume in 1 s. The US Food and Drug Administration's recommendation to use an anti-interleukin-5 antibody for the treatment of severe eosinophilic asthma suggests that there will be a therapeutic place for these anti-Th2 agents. Biomarkers should be used to identify the right patients for such targeted approaches. More guidance will be needed as to which patients should receive each of these classes of selective antibody-based treatments. Currently, there is no treatment that targets the cytokines driving asthma associated with non-eosinophilic inflammation and low Th2 expression.
authors.affiliation: Experimental Studies, Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK; National Institute for Health Research (NIHR), Respiratory Biomedical Research Unit, Royal Brompton & Harefield NHS Trust and Imperial College London, London, UK. Electronic address: f.chung@imperial.ac.uk.
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
mesh_terms: D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007378:Interleukins / Q000037:antagonists & inhibitors*; D058990:Molecular Targeted Therapy / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects
chemical_list: D018927:Anti-Asthmatic Agents; D007378:Interleukins