Intracerebroventricular administration of bacterial lipopolysaccharide prevents the development of acute experimental pancreatitis in the rat.

摘要

BACKGROUND: Lipopolysaccharides (LPS) are responsible for septic shockbut low doses of LPS reduce pancreatic damage produced by caerulein-induced pancreatitis (CIP) in rats.Leptin, produced by adipocytes attenuates the severity of CIP. The aim of this study was to evaluatethe effect of intracerebroventricular (i.c.v.) administration of LPS on CIP and plasma leptin level andto investigate the involvement of sensory nerves (SN) in the effects of LPS on CIP. MATERIAL/METHODS:CIP was produced by subcutaneous (s.c.) infusion of caerulein (25 Kg/kg) to conscious rats. SN were deactivatedwith capsaicin (100 mg/kg s.c.). LPS (0.2, 2, or 20 Kg/rat) were applied to the right cerebral ventricle30 min prior to CIP. RESULTS: CIP was manifested by an increase in plasma levels of amylase, lipase,leptin and an anti-inflammatory interleukin 10 (IL-10), (by 400%, 1000%, 700% and 50%, respectively),confirmed by histological examination and accompanied by 40% reduction in pancreatic blood flow. Pretreatmentof CIP rats with i.c.v. LPS resulted in significant reduction of CIP accompanied by dose-dependent increasein plasma levels of leptin and IL-10. Deactivation of SN, which by itself failed to affect CIP, completelyreversed the beneficial effects of i.c.v. administration of LPS on CIP and reduced plasma leptin andIL-10 concentrations. CONCLUSIONS: Pretreatment with LPS given i.c.v. prevents the development of caerulein-inducedpancreatitis through the activation of SN and though the release of leptin.