Pneumologie 2011; 65 - A66
DOI: 10.1055/s-0031-1296157

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

M Wegmann 1, L Lunding 1, Z Orinska 2, DM Wong 3, RA Manz 3, H Fehrenbach 1
  • 1Bereich Experimentelle Pneumologie, Forschungszentrum Borstel
  • 2Abteilung für Immunologie, Forschungszentrum Borstel
  • 3Institut für Systemische Entzündungsforschung (ISEF), Universität Lübeck

Introduction: Since allergen-specific immuno-globulin E (IgE) enables mast cells and eosinophils to react on allergen-contact it plays a critical role in the formation of allergic inflammation and has been identified as a target for asthma therapy. By inhibiting the proteasome complex Bortezomib efficiently depletes Ig-secreting plasma cells and, thus, reduces Ig-serum titers. The present study evaluates the therapeutic potential of Bortezomib in a mouse model of chronic experimental asthma.

Methods: Therefore, Mice were sensitized to ovalbumin (OVA) and challenged with OVA-aerosol for twelve weeks. Bortezomib treatment was started after six weeks of challenge, and continued for one week (short-term) or six weeks (long-term), respectively, with a dosage of 0.75mg/kg body weight with two intra-venous injections weekly. Lung function, lung histology, Ig serum titers, and plasma cell numbers were assessed.

Results: In mice with chronic experimental asthma short-term treatment resulted in decreased eosinophil numbers in BAL fluids, while long-term treatment significantly lowered serum titers of anti-OVA IgE. Nevertheless, neither short-term nor long-term treatment significantly diminished plasma cell numbers, anti-OVA IgG1 serum titers, allergic airway inflammation or improved lung function.

Discussion: These results demonstrate that Bortezomib has no therapeutic effect on chronic experimental asthma in mice. Therefore, Bortezomib treatment could have only limited value as plasma cell depleting therapy against allergic bronchial asthma.