title: Th2 cytokine antagonists: potential treatments for severe asthma.
abstract: BACKGROUND
  Asthma is a major disease burden worldwide. Treatment with steroids and long acting β-agonists effectively manage symptoms in many patients but do not treat the underlying cause of disease and have serious side effects when used long term and in children. Therapies targeting the underlying causes of asthma are urgently needed. T helper type 2 (Th2) cells and the cytokines they release are clinically linked to the presentation of all forms of asthma. They are the primary drivers of mild to moderate and allergic asthma. They also play a pathogenetic role in exacerbations and more severe asthma though other factors are also involved. Much effort using animal models and human studies has been dedicated to the identification of the pathogenetic roles of these cells and cytokines and whether inhibition of their activity has therapeutic benefit in asthma.
  
  
  METHODS
  We discuss the current status of Th2 cytokine antagonists for the treatment of asthma. We also discuss the potential for targeting Th2-inducing cytokines, Th2 cell receptors and signaling as well as the use of Th2 cell antagonists, small interfering oligonucleotides, microRNAs, and combination therapies.
  
  
  CONCLUSIONS
  Th2 antagonists may be most effective in particular asthma subtypes/endotypes where specific cytokines are known to be active through the analysis of biomarkers. Targeting common receptors and pathways used by these cytokines may have additional benefit. Animal models have been valuable in identifying therapeutic targets in asthma, however the results from such studies need to be carefully interpreted and applied to appropriately stratified patient cohorts in well-designed clinical studies and trials.
authors.affiliation: The University of Newcastle, Priority Research Centre for Asthma and Respiratory Disease and Hunter Medical Research Institute, Level 2, Kookaburra Circuit, New Lambton Heights, Newcastle, New South Wales, 2305, Australia. Philip.Hansbro@newcastle.edu.au
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hansbro
authors.forename: Grace V
authors.initials: GV
authors.lastname: Scott
authors.forename: Ama-Tawiah
authors.initials: AT
authors.lastname: Essilfie
authors.forename: Richard Y
authors.initials: RY
authors.lastname: Kim
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Starkey
authors.forename: Duc H
authors.initials: DH
authors.lastname: Nguyen
authors.forename: Paul D
authors.initials: PD
authors.lastname: Allen
authors.forename: Gerard E
authors.initials: GE
authors.lastname: Kaiko
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Jay C
authors.initials: JC
authors.lastname: Horvat
authors.forename: Paul S
authors.initials: PS
authors.lastname: Foster
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D018418:Th2 Cells / Q000276:immunology
chemical_list: D018927:Anti-Asthmatic Agents; D016207:Cytokines