1. The effects of the inhaled
corticosteroid budesonide and a novel
PDE 4 inhibitor CDP840 given systematically, were evaluated in a model of
antigen-induced airway
inflammation in the rabbit. 2. Adult litter-matched NZW rabbits (2.4-3.5 kg) immunised within 24 h of birth with Alternaria tenuis
antigen were pretreated with
budesonide (total dose 100 micrograms, inhaled over 2 days) or
CDP840 (total dose 7 mg kg-1, i.p. over 3 days), before
antigen challenge. For each
drug-treated group a parallel group of rabbits was pretreated with the appropriate vehicle. In all groups airway responsiveness to inhaled
histamine was assessed and bronchoalveolar lavage (BAL) performed 24 h before and after
antigen challenge. 3. Basal lung function in terms of total lung resistance (RL; cmH2O l 1s-1) and dynamic compliance (Cdyn; ml cmH2O-1) were unaltered by pretreatment with
budesonide or
CDP840 compared to their respective vehicles 24 h before or after
antigen challenge. 4. The RL component of the acute bronchoconstriction induced by inhaled Alternaria tenuis
aerosol was unaffected by pretreatment with
budesonide. However,
budesonide prevented the fall in Cdyn due to
antigen. Treatment with
CDP840 significantly reduced
antigen-induced acute bronchoconstriction in terms of both RL and Cdyn. 5.
Airway hyperresponsiveness (AHR) to inhaled
histamine was indicated by reduced RL PC50 (2.4-4.5 fold) and Cdyn PC35 (2.1-3.9 fold) values 24 h after
antigen challenge. Treatment with either
budesonide or
CDP840 abolished the
antigen-induced increase in responsiveness to inhaled
histamine. 6. Total cells recovered per ml of BAL fluid increased 24 h after
antigen challenge.
Antigen-induced
pulmonary eosinophilia was reduced (93%) in
budesonide and (85%) in
CDP840 treated rabbits.
Antigen-induced increases in neutrophil numbers were reduced (76%) with
budesonide but not
CDP840 pretreatment. 7. Inhalation of Alternaria tenuis
aerosol elicited an acute bronchoconstriction, followed 24 hours later by an increased responsiveness to inhaled
histamine and pulmonary neutrophil and eosinophil recruitment.
CDP840 was more effective than
budesonide in preventing the
antigen-induced increase in total lung resistance (RL); however, both drugs prevented the
antigen-induced reduction in dynamic compliance (Cdyn).
CDP840 and
budesonide also prevented
antigen-induced AHR and
eosinophilia in the immunised rabbit.