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Am. J. Respir. Cell Mol. Biol., Volume 19, Number 4, October, 1998 622-628

Allergen Immunotherapy Inhibits Airway Eosinophilia and Hyperresponsiveness Associated with Decreased IL-4 Production by Lymphocytes in a Murine Model of Allergic Asthma

Antoon J. M. Van Oosterhout, Betty Van Esch, Gerard Hofman, Claudia L. Hofstra, Ingrid Van Ark, Frans P. Nijkamp, Martien L. Kapsenberg, Huub F. J. Savelkoul, and Frank R. Weller

Department of Pharmacology and Pathophysiology, Utrecht University, Utrecht; Laboratory of Cell Biology and Histology, Academic Medical Center, Amsterdam; Department of Immunology, Erasmus University, Rotterdam; and Department of Pulmonology, Academic Medical Center, Amsterdam, The Netherlands

In the present study, we investigated whether allergen immunotherapy is effective in a murine model with immunologic and pathophysiologic features reminiscent of allergic asthma. Ovalbumin-sensitized mice received increasing (1 µg to 1 mg) subcutaneous doses of ovalbumin twice a week for 8 wk according to a semirush immunotherapy protocol as used in allergic patients. During immunotherapy, an initial rise in serum levels of ovalbumin-specific antibodies (immunoglobulin [Ig]G1, IgE, IgG2a) occurred, after which IgE levels decreased sharply concomitant with an increase in IgG2a levels. The increase in IgG2a levels, with the decline in IgE levels, suggests that during immunotherapy interferon-gamma production is increased or interleukin (IL)-4 production is decreased. After immunotherapy, inhalation challenge of the mice with ovalbumin revealed almost complete inhibition (98%, P < 0.01) of eosinophil infiltration into bronchoalveolar lavage and airway hyperresponsiveness (100% at 320 µg/kg methacholine, P < 0.05) compared with sham-treated animals. In addition, IL-4 production of thoracic lymph node cells stimulated with ovalbumin in vitro was largely reduced (60%, P < 0.05) after immunotherapy. Thus, effective immunotherapy in this animal model appears to be due to modulation of antigen-specific T cells. Similar effects on airway symptoms and IL-4 production can be obtained within 1 wk by three injections of the highest dose of ovalbumin (1 mg). This animal model will be used as a preclinical model to improve allergen immunotherapy and to gain more insight into the mechanisms involved.




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Copyright © 1998 American Thoracic Society. 		  2009/2010 ATS Fellows Career Development Awards