CYTOKINE-INDUCED NEUTROPHIL CHEMOATTRACTANT
Springer Online Journal Archives 1860-2000
Abstract The therapeutic effects of an intravenouslyinjected carboxamide derivative (IS-741) on lung injurywere studied in rats with cerulein-induced pancreatitiscomplicated by endotoxemia. Pancreatitis was induced by four intramuscular injections of cerulein(50 μg/kg at 1-hr intervals). Pancreatitis rats wereinjected intraperitoneally with 10 mg/kg oflipopolysaccharide (LPS) 6 hr following the firstcerulein injection as a challenge of endotoxemia. Ratswere divided into four groups: group I, pancreatitiswith LPS; group II, pancreatitis with LPS treated witha continuous intravenous injection of IS-741 at 0.03 mg/kg/hr); group III, pancreatitis withLPS treated with a continuous intravenous injection ofIS-741 at 0.3 mg/kg/hr); and group IV, pancreatitis withLPS treated with a continuous intravenous injection of IS-741 at 3 mg/kg/hr). IS-741 wasadministered 30 min before the endotoxemia challenge.Intense mononuclear cell infiltration and lunghemorrhage occurred in untreated pancreatitis rats withLPS (group I), but hemorrhage was not seen in group IVrats receiving a continuous injection of IS-741 shortlybefore the induction of endotoxemia. The IS-741- treatedrats (groups II, III, and IV) had lower serum concentrations of cytokine-induced neutrophilchemoattractant (CINC), as well as fewer pulmonaryinfiltrates immunoreactive for CINC or Mac-1(CD11b/CD18). The number of neutrophils infiltrating thelung in groups II, III, and IV was significantlylower than that of group I. Conversely, CINC productionby bronchoalveolar macrophages in vitro were stimulatedby LPS but were reduced by the presence of IS-741. The carboxamide derivative IS-741 effectivelyprevented pancreatitisassociated lung injury followingthe challenge of endotoxemia.
Type of Medium: