Effects of neonatal immunization and repeated allergen exposure on airway responsiveness in the rabbit.
Neonatal immunization of rabbits has previously been shown to enhance airway responsiveness to inhaled histamine. We investigated the influence of this immunization protocol on pulmonary parameters after inhalation of histamine in littermate allergen-immunized, sham-immunized, and saline-injected rabbits. In spontaneously breathing rabbits, inhalation of histamine caused a concentration-dependent increase in total lung resistance (RL) and respiratory rate (RR) and a reduction in dynamic compliance (Cdyn). Allergen-immunized rabbits were significantly more responsive to histamine than their control littermates and saline-injected animals when the concentration-effect curves were analyzed in terms of changes in RL (P < 0.05), Cdyn (P < 0.05), and RR (P < 0.05) among these groups. The production of allergen-specific immunoglobulins in this model was not correlated to indexes of airway responsiveness (P > 0.05). The effect of inhaled AMP on pulmonary function in allergen-immunized and native animals was also examined. Inhalation of AMP failed to influence Cdyn but elicited significant non-concentration-dependent increases in total RL in allergen-immunized but not naive animals (P < 0.05). Inhalation of AMP also caused a concentration-dependent increase in RR in both allergen-immunized and naive rabbits that was not significantly different (P > 0.05). The influence of biweekly exposure to inhaled or systemic allergen in allergen-immunized rabbits was also examined. Neither repeated systemic nor aerosolized allergen exposure of neonatally immunized rabbits from 3 to 7 mo of age resulted in a further enhancement of airway responsiveness to inhaled histamine. These results suggest that neonatal immunization with Alternaria allergens enhances airway responsiveness to inhaled histamine and AMP. This airway hyperresponsiveness at 3 mo of age could not be enhanced further after chronic exposure to allergen.
Minshall
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Sackler Institute of Pulmonary Pharmacology, King's College Hospital School of Medicine and Dentistry, London, United Kingdom.
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D000241:Adenosine / Q000494:pharmacology*; D000403:Airway Resistance / Q000187:drug effects*; D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology*; D007114:Immunization; D011817:Rabbits; D012119:Respiration / Q000187:drug effects*
D000485:Allergens; D006632:Histamine; D000241:Adenosine