Allergen immunotherapy inhibits airway eosinophilia and hyperresponsiveness associated with decreased IL-4 production by lymphocytes in a murine model of allergic asthma.
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 microgram 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 microgram/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.
Van Oosterhout
A J
AJ
Department of Pharmacology and Pathophysiology, Utrecht University, Utrecht, The Netherlands. A.J.M.VanOosterhout@far.ruu.nl
Van Esch
B
B
Hofman
G
G
Hofstra
C L
CL
Van Ark
I
I
Nijkamp
F P
FP
Kapsenberg
M L
ML
Savelkoul
H F
HF
Weller
F R
FR
D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology / Q000628:therapy*; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000378:metabolism
D016085:Bronchoconstrictor Agents; D007074:Immunoglobulin G; D016210:Methacholine Chloride; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin