title: Efficacy of soluble IL-4 receptor for the treatment of adults with asthma.
abstract: BACKGROUND
  IL-4 mediates important proinflammatory functions in asthma, including induction of the IgE isotype switch, increased expression of vascular cell adhesion molecule 1 and promotion of eosinophil transmigration across the endothelium, stimulation of mucus production, and T(H)2 lymphocyte differentiation, leading to release of IL-4, IL-5, IL-9, and IL-13.
  
  
  OBJECTIVE
  The current study evaluated the therapeutic potential of inhaled recombinant human soluble interleukin-4 receptor (IL-4R) as an IL-4 antagonist.
  
  
  METHODS
  This study was a randomized, double-blind, placebo-controlled study in 62 subjects involving 12 once weekly nebulizations of 0.75, 1.5, or 3.0 mg of IL-4R or placebo. During screening, subjects documented dependence on inhaled corticosteroids by an exacerbation in asthma induced by one or two 50% dose reductions at 2-week intervals. After restabilization for 2 weeks on the dose above which their asthma flared, inhaled steroids were discontinued, patients were randomized, and study medication was started on day 0.
  
  
  RESULTS
  IL-4R was well tolerated. Efficacy was demonstrated by a decline in FEV(1) observed in the placebo group (-0.4 L and -13% predicted), which did not occur in the group receiving 3.0 mg of IL-4R (-0.1 L and -2% predicted; P =.05 over the 3-month treatment period). Daily patient-measured morning FEV(1) also demonstrated a significant decline in the placebo group (-0.5 L and -18% predicted), which did not occur in the group receiving 3.0 mg of IL-4R (-0.1 L and -4% predicted; P =.02 over the 3-month treatment period). The efficacy of IL-4R was further confirmed by the absence of increase in asthma symptom scores in the group receiving 3.0 mg of IL-4R (Delta 0.1) compared with that seen in the placebo group (Delta 1.4 over 1 month; P =.07). Study discontinuation for asthma exacerbation was not significantly different between groups (placebo, 56%; 3.0 mg of IL-4R, 47%; P = not significant).
  
  
  CONCLUSIONS
  These promising data suggest that IL-4R is safe and effective in the treatment of moderate persistent asthma.
authors.affiliation: National Jewish Medical and Research Center, University of Colorado, Health Sciences Center, Denver, CO, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Borish
authors.forename: H S
authors.initials: HS
authors.lastname: Nelson
authors.forename: J
authors.initials: J
authors.lastname: Corren
authors.forename: G
authors.initials: G
authors.lastname: Bensch
authors.forename: W W
authors.initials: WW
authors.lastname: Busse
authors.forename: J B
authors.initials: JB
authors.lastname: Whitmore
authors.forename: J M
authors.initials: JM
authors.lastname: Agosti
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D019948:Receptors, Interleukin-4 / Q000097:blood / Q000235:genetics / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012995:Solubility
chemical_list: D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins; D015847:Interleukin-4