A canine model for the study of hapten-specific suppression of IgE-mediated bronchoconstriction and anaphylaxis.
Newborn mongrel dogs were sensitized with conjugates of ovalbumin (OA) and 2,4-dinitrophenol (OA-DNP3) in the presence of Al(OH)3 to produce high levels of anti-OA and anti-DNP IgE antibody. At 4-6 months of age, when anti-DNP and anti-OA antibody levels reached titers of 64 by passive cutaneous anaphylaxis, the dogs underwent separate inhalation and intravenous challenges with conjugates of DNP and bovine gamma globulin (DNP15-BGG) and OA. Inhalation challenge with DNP15-BGG and OA resulted in 5- and 10-fold increases in airflow resistance, respectively. Intravenous challenge with either DNP15-BGG or OA produced profound anaphylaxis with 60-80% decreases in blood pressure, cardiac output and regional blood flows in the carotid, superior mesenteric and renal arteries, and the distal aorta. Treatment of sensitized dogs with 5 doses of 20 mg of conjugates of DNP and polyvinyl alcohol (DNP2-PVA) on alternate days resulted in suppression of anti-DNP IgE antibody production; abrogation of established airway and vascular anaphylactic sensitivities; no change in regional blood flows, and no effect on sensitivities to challenge with OA.
D019297:2,4-Dinitrophenol; D000707:Anaphylaxis / Q000209:etiology*; D000818:Animals; D001985:Bronchial Provocation Tests; D001986:Bronchial Spasm / Q000209:etiology*; D004140:Dinitrophenols / Q000494:pharmacology* / Q000633:toxicity; D004195:Disease Models, Animal / Q000276:immunology*; D004285:Dogs / Q000276:immunology*; D006241:Haptens / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007165:Immunosuppression Therapy / Q000379:methods*; D010047:Ovalbumin / Q000633:toxicity; D012039:Regional Blood Flow / Q000187:drug effects
D004140:Dinitrophenols; D006241:Haptens; D007073:Immunoglobulin E; D010047:Ovalbumin; D019297:2,4-Dinitrophenol