Interleukin-4 receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial

Am J Respir Crit Care Med. 1999 Dec;160(6):1816-23. doi: 10.1164/ajrccm.160.6.9808146.


Interleukin-4 mediates important proinflammatory functions in asthma, including induction of the IgE isotype switch, expression of VCAM-1 on endothelium, mucin production, 15-lipoxygenase activity, and Th2 lymphocyte stimulation leading to the secondary synthesis of IL-4, IL-5, and IL-13. Soluble recombinant human IL-4 receptor (IL-4R; Nuvance; altrakincept) inactivates naturally occurring IL-4 without mediating cellular activation. Nebulized IL-4R has a serum half-life of approximately 1 wk. In this double-blind, placebo-controlled trial, 25 patients with moderate asthma requiring inhaled corticosteroids were randomly assigned to receive a single nebulized dose of IL-4R 1,500 microg, IL-4R 500 microg, or placebo after stopping inhaled corticosteroids. No drug-related toxicity was observed. Treatment with IL-4R produced significant improvement in FEV(1) on Day 4 (1,500 microg versus placebo; p < 0.05) and in FEF(25-75) on Days 2 and 4 (1,500 microg versus placebo; p < 0.05). Asthma symptom scores stabilized among patients treated with IL-4R 1, 500 microg, despite abrupt withdrawal of corticosteroids, but not in the IL-4R 500 microg group or the placebo group (p < 0.05). Patients in the IL-4R 1,500 microg group also required significantly less beta(2)-agonist rescue use (p < 0.05). Anti-inflammatory effects were further demonstrated by significantly reduced exhaled nitric oxide (p < 0.05).

Conclusions: A single dose of IL-4R appears safe and effective in moderate asthma. The 1,500 microg dose appears as safe but significantly more effective than the 500 microg dose.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Aged
  • Asthma / drug therapy*
  • Asthma / immunology
  • Asthma / physiopathology
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume
  • Humans
  • Hypersensitivity, Immediate / complications*
  • Immunoglobulin E / blood
  • Intercellular Adhesion Molecule-1 / blood
  • Male
  • Maximal Midexpiratory Flow Rate
  • Middle Aged
  • Nebulizers and Vaporizers
  • Peak Expiratory Flow Rate
  • Quality of Life
  • Receptors, Interleukin-4 / administration & dosage*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Vascular Cell Adhesion Molecule-1 / blood


  • Receptors, Interleukin-4
  • Recombinant Proteins
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Immunoglobulin E