EFFECTS OF CAPSAICIN ON THE AIRWAY RESPONSES TO INHALED ENDOTOXIN IN THE GUINEA-PIG

Inhalation of lipopolysaccharide (LPS) has been associated with increa sed airway responsiveness and inflammation both in humans and in anima ls. To investigate the contribution of capsaicin-sensitive nerves to t hese changes, we compared airway responsiveness and inflammation after intratracheal administration of 10 mu g/kg LPS (Escherichia coli O55: B5 lipopolysaccharide) or saline in guinea pigs treated 10 days previo usly with 50 mg/kg capsaicin and in those pretreated with the capsaici n vehicle. Four hours after LPS, airway responsiveness and cell counts in the bronchoalveolar lavage were assessed. To determine airway resp onsiveness, guinea pigs were anesthetized, tracheotomized, and mechani cally ventilated before exposure to increasing concentrations of aeros olized histamine (10(-4) to 10(-3) M). Capsaicin pretreatment prevente d the LPS-induced increase in airway responsiveness in response to aer osolized histamine. It significantly reduced total cell recovery in th e bronchoalveolar lavage after LPS(1,167 +/- 167 10(3) cells/ml in cap saicin-treated guinea pigs versus 2,171 +/- 184 10(3) in vehicle-treat ed guinea pigs) by reducing the LPS-induced influx of neutrophils and macrophages. Additional experiments demonstrated that the activity of neutral endopeptidase (NEP) in the tracheal epithelium was not signifi cantly different in guinea pigs injected with LPS from that in the sal ine-treated control animals, and that the pretreatment with the NEP in hibitor phosphoramidon did not increase the LPS-induced influx of neut rophils into the bronchoalveolar lavage. These results demonstrate tha t in the guinea pig, capsaicin-sensitive nerves are involved in LPS-in duced airway hyperresponsiveness and inflammation.