Am. J. Respir. Crit. Care Med., Vol 149, No. 1, Jan 1994, 128-133.
Effects of capsaicin on the airway responses to inhaled endotoxin in the guinea pig
PH Jarreau, MP D'Ortho, V Boyer, A Harf and I Macquin-Mavier
Departement de Physiologie, Faculte de Medecine, Creteil, France.
Inhalation of lipopolysaccharide (LPS) has been associated with increased
airway responsiveness and inflammation both in humans and in animals. To
investigate the contribution of capsaicin-sensitive nerves to these
changes, we compared airway responsiveness and inflammation after
intratracheal administration of 10 micrograms/kg LPS (Escherichia coli
O55:B5 lipopolysaccharide) or saline in guinea pigs treated 10 days
previously with 50 mg/kg capsaicin and in those pretreated with the
capsaicin vehicle. Four hours after LPS, airway responsiveness and cell
counts in the bronchoalveolar lavage were assessed. To determine airway
responsiveness, guinea pigs were anesthetized, tracheotomized, and
mechanically ventilated before exposure to increasing concentrations of
aerosolized histamine (10(-4) to 10(-3) M). Capsaicin pretreatment
prevented the LPS-induced increase in airway responsiveness in response to
aerosolized histamine. It significantly reduced total cell recovery in the
bronchoalveolar lavage after LPS (1,167 +/- 167 10(3) cells/ml in
capsaicin-treated guinea pigs versus 2,171 +/- 184 10(3) in vehicle-treated
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
significantly different in guinea pigs injected with LPS from that in the
saline-treated control animals, and that the pretreatment with the NEP
inhibitor phosphoramidon did not increase the LPS-induced influx of
neutrophils into the bronchoalveolar lavage. These results demonstrate that
in the guinea pig, capsaicin- sensitive nerves are involved in LPS-induced
airway hyperresponsiveness and inflammation.
