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- Title
The Novel Carboxamide Derivative IS-741 Reduces Neutrophil Chemoattractant Production by Bronchoalveolar Macrophages in Rats with Cerulein-Induced Pancreatitis Complicated by Sepsis.
- Authors
Yamaguchi, Yasuo; Okabe, Kazutoshi; Jian Liang; Matsumura, Fujio; Akizuki, Eiji; Matsuda, Teishi; Ohshiro, Hajime; Nakano, Shogo; Ishihara, Kohjiroh; Ogawa, Michio
- Abstract
Background/Aims: The priming mechanism of macrophages to secrete cytokines in acute pancreatitis is important for remote organ failure following septic complication. The effects of novel carboxamide derivative, IS-741, on neutrophil chemoattractant production by bronchoalveolar macrophages were studied in rats with cerulein-induced pancreatitis complicated by sepsis. Methods: Pancreatitis was induced by four intramuscular injections of cerulein (50 μg/kg at 1-hour intervals). Pancreatitis rats were injected intraperitoneally with 10 mg/kg of lipopolysaccharide (LPS) 6 h following the first cerulein injection as a septic challenge. Pancreatitis rats received a continuous intravenous injection of IS-741 (3 mg/kg/h) 30 min before the septic challenge. Results: Intense mononuclear cell infiltration and lung hemorrhage occurred in untreated pancreatitis rats complicated with sepsis, but hemorrhage was not seen in septic pancreatitis rats receiving a continuous intravenous injection of IS-741 shortly before sepsis induction. The IS-741-treated rats had lower serum concentrations of cytokine-induced neutrophil chemoattractant (CINC), as well as fewer the pulmonary neutrophils and infiltrates immunoreactive for CINC or Mac-1 (CD11b/CD18). Conclusion: The novel carboxamide derivative IS-741 reduced CINC production by bronchoalveolar macrophages and effectively prevented pancreatitis-associated lung injury following the septic challenge.
- Subjects
NEUTROPHILS; BRONCHOALVEOLAR lavage; MACROPHAGES; SEPSIS; DISEASE complications
- Publication
Digestion, 1999, Vol 60, p52
- ISSN
0012-2823
- Publication type
Article
- DOI
10.1159/000051454