Allergen immunotherapy inhibits airway eosinophilia and hyperresponsiveness associated with decreased IL-4 production by lymphocytes in a murine model of allergic asthma

A.J.M. van Oosterhout, B. van Esch, G. Hofman, C.L. Hofstra, I. van Ark, F.P. Nijkamp, M.L. Kapsenberg, H.F.J. Savelkoul, F.R. Weller

Research output: Contribution to journalArticleAcademicpeer-review

46 Citations (Scopus)

Abstract

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 ?g 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- production is increased or interleukin (IL)-4 production is decreased. After immunotherapy, inhalation challenge of the mice with ovalbumin revealed almost complete inhibition (98 percent, P < 0.01) of eosinophil infiltration into bronchoalveolar lavage and airway hyperresponsiveness (100 percent at 320 ?g/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 percent, 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
Original languageEnglish
Pages (from-to)622-628
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume19
Issue number4
DOIs
Publication statusPublished - 1998
Externally publishedYes

Fingerprint Dive into the research topics of 'Allergen immunotherapy inhibits airway eosinophilia and hyperresponsiveness associated with decreased IL-4 production by lymphocytes in a murine model of allergic asthma'. Together they form a unique fingerprint.

Cite this