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

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

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  • 1Bereich Experimentelle Pneumologie, Forschungszentrum Borstel, Borstel, Deutschland. mwegmann@fz-borstel.de

Abstract

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.

Copyright © 2011 S. Karger AG, Basel.

[PubMed - indexed for MEDLINE]
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