RESUMO
Corticosteroids are known to inhibit bronchial hyperresponsiveness (BHR) and allergic inflammation but there is little information on its dose-dependence. We examined the effect of different doses of the glucocorticosteroid budesonide in an allergic model. Brown-Norway rats were sensitised to ovalbumin (OVA) and pretreated with an intra-gastric dose of budesonide (0.1, 1.0, or 10 mgkg(-1)). Exposure to OVA induced BHR, accumulation of eosinophils in the bronchoalveolar lavage (BAL) fluid and in the airways submucosa. Budesonide dose-dependently inhibited BAL fluid influx of lymphocytes, eosinophils and neutrophils, tissue eosinophils and lymphocytes and BHR. At 0.1 mgkg(-1), budesonide did not inhibit these parameters but at 1 mgkg(-1), BAL fluid eosinophils and T-cells, and submucosal T-cells were significantly reduced. At 10 mgkg(-1), budesonide suppressed BHR, BAL fluid inflammatory cells numbers and tissue eosinophilia. T-cell numbers were more related to BHR than eosinophil numbers. Budesonide inhibited both airway inflammation and BHR, but BAL fluid eosinophil cell counts may be dissociated from BHR.
Assuntos
Hiper-Reatividade Brônquica/prevenção & controle , Budesonida/uso terapêutico , Glucocorticoides/uso terapêutico , Hipersensibilidade/prevenção & controle , Acetilcolina/efeitos adversos , Animais , Contagem de Células Sanguíneas , Hiper-Reatividade Brônquica/imunologia , Testes de Provocação Brônquica , Líquido da Lavagem Broncoalveolar/citologia , Budesonida/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Glucocorticoides/administração & dosagem , Hipersensibilidade/imunologia , Masculino , Ovalbumina/imunologia , RatosRESUMO
BACKGROUND: Cough reflex can be induced by the pepper extract capsaicin and by low pH in guinea-pig airways. Transient receptor potential vanniloid-1 (TPRV-1) is expressed in the sensory and afferent nerve fibres in airways. OBJECTIVE: We hypothesized that a novel pyridazinylpiperazine analog TPRV-1 inhibitor can effectively reduce cough reflex stimulated by citric acid and capsaicin. METHODS: Guinea pigs were injected with specific TPRV-1 inhibitor, V112220, a pyridazinylpiperazine analog of N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl) tetrahydropyrazine-1(2H)-carbox-amide (BCTC) (3 mg/kg) intra-peritoneally. One hour before cough response assessment. Coughs were recorded using a recorder system that identified cough sound and accompanying expiratory flows, distinct from sneezes. Guinea-pigs exposed to citric acid (0.4 M) and to capsaicin (10-4M) aerosols, in succession separately by 2 hours. RESULTS: V112220 significantly inhibited the number of coughs induced by citric acid (73 +/- 11%, p < 0.01) and capsaicin (70 +/- 9.4%, p < 0.05) compared to vehicle control. CONCLUSION: A novel pyridazinylpiperazine analog TPRV-1 inhibitor can inhibit the cough reflex, induced by both low pH and capsaicin, suggesting that it could be clinically beneficial in treatment of cough.