Effects of ketotifen on airway responses to allergen challenge in the actively sensitized brown Norway rat.
The purpose of the study was to examine the effect of ketotifen on the airway responses and the recruitment of the inflammatory cells into the airways of sensitized rats after antigen challenge. Twenty-five Brown Norway rats, 7-9 weeks old, were actively sensitized to ovalbumin (OA) (1 mg s.c.) and Bordetella pertussis vaccine (10(9) bacilli i.p.). At 14 days after sensitization rats were anesthetized with urethane (1.1 g/kg i.p.) and intubated endotracheally. Aerosols of OA (5% W/V in saline for 5 min) were administered to control rats (Group A; n = 9), to a low-dose ketotifen group (Group B; 1 mg/kg PO; n = 8) and a high-dose ketotifen group (Group C; 10 mg/kg; PO for 10 days; n = 9). Pulmonary resistance (RL) was measured at baseline, and every 15 min for up to 8 h after OA. The magnitude of the early response was 241 +/- 51% in A (% baseline RL; mean +/- SE), and significantly less in B(119 +/- 7%) and C(131 +/- 16%) (p < 0.01). The late response was significantly lower in C than A but not B. The total cell number in bronchoalveolar lavage at 8 h after OA challenge was significantly higher in A than B and C (p < 0.01). The lymphocyte and eosinophil counts were reduced in B and C compared to A (p < 0.05). A positive correlation was found between the late response and total number of cells recovered in the BAL (r = 0.78) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Sapienza
S
S
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Renzi
P M
PM
Martin
J G
JG
D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D007073:Immunoglobulin E / Q000276:immunology; D007665:Ketotifen / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D010567:Pertussis Vaccine / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D012137:Respiratory System / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology
D000336:Aerosols; D000485:Allergens; D010567:Pertussis Vaccine; D012701:Serotonin; D007073:Immunoglobulin E; D010047:Ovalbumin; D007665:Ketotifen