Long-term bortezomib treatment reduces allergen-specific IgE but fails to ameliorate chronic asthma in mice

Int Arch Allergy Immunol. 2012;158(1):43-53. doi: 10.1159/000330103. Epub 2011 Dec 29.


Background: Allergen-specific immunoglobulin (Ig) E initiates the effector cascade of allergic asthma and has been identified as a valuable target for therapeutic treatment of this disease. The proteasome inhibitor bortezomib was previously shown to deplete Ig-secreting plasma cells and to efficiently suppress Ig serum titers. The present study aimed at evaluating the therapeutic potential of the proteasome inhibitor bortezomib in allergic bronchial asthma.

Methods: To address this question, a chronic experimental asthma mouse model was used in a therapeutic setting. Mice were sensitized to ovalbumin (OVA) and challenged with OVA aerosol for 12 weeks. After 6 weeks of challenge, bortezomib treatment was started and continued for 1 week (short-term) or 6 weeks (long-term) with a dosage of 0.75 mg/kg body weight twice a week. Lung function, lung histology, Ig serum titers and plasma cell numbers were assessed.

Results: Whereas short-term treatment lowered bronchoalveolar lavage eosinophils, long-term treatment considerably reduced serum titers of anti-OVA IgE in mice with chronic experimental asthma. However, neither short-term nor long-term treatment significantly reduced plasma cell numbers, anti-OVA IgG1 serum titers or allergic airway inflammation or ablated airway hyperresponsiveness.

Conclusion: Our results suggest that bortezomib treatment has only limited value as plasma cell-depleting therapy against allergic bronchial asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology*
  • Animals
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / immunology
  • Asthma / physiopathology
  • Boronic Acids / therapeutic use*
  • Bortezomib
  • Chronic Disease
  • Disease Models, Animal
  • Eosinophils / drug effects
  • Eosinophils / immunology
  • Female
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology*
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Lung / immunology
  • Lung / pathology
  • Lung / physiopathology
  • Mice
  • Mice, Inbred BALB C
  • Plasma Cells / drug effects
  • Plasma Cells / immunology
  • Pyrazines / therapeutic use*
  • Treatment Failure


  • Allergens
  • Anti-Asthmatic Agents
  • Boronic Acids
  • Immunoglobulin G
  • Pyrazines
  • Immunoglobulin E
  • Bortezomib