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 influe nce of this immunization protocol on pulmonary parameters after inhala tion of histamine in littermate allergen-immmunized, sham-immunized, a nd saline-injected rabbits. In spontaneously breathing rabbits, inhala tion of histamine caused a concentration-dependent increase in total l ung resistance (RL) and respiratory rate (RR) and a reduction in dynam ic compliance (Cdyn). Allergen-immunized rabbits were significantly mo re responsive to histamine than their control littermates and saline-i njected 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 immunoglobulin s in this model was not correlated to indexes of airway responsiveness P > 0.05). The effect of inhaled AMP on pulmonary function in allerge n-immunized and naive animals was also examined. Inhalation of AMP fai led to influence Cdyn but elicited significant non-concentration-depen dent increases in total RL in allergen-immunized but not naive animals (P < 0.05). Inhalation of AMP also caused a concentration-dependent-i ncrease in RR in both allergen-immunized and naive rabbits that was no t significantly different (P > 0.05). The influence of biweekly exposu re to inhaled or systemic allergen in allergen-immunized rabbits was a lso examined. Neither repeated systemic nor aerosolized allergen expos ure of neonatally immunized rabbits from 3 to 7 mo of age resulted in a further enhancement of airway responsiveness to inhaled histamine. T hese results suggest that neonatal immunization with Alternaria allerg ens enhances airway responsiveness to inhaled histamine and AMP. This airway hyperresponsiveness at 3 mo of age could not be enhanced furthe r after chronic exposure to allergen.