Intracerebroventricular administration of bacterial lipopolysaccharide prevents the development of acute experimental pancreatitis in the rat.
BACKGROUND
Lipopolysaccharides (LPS) are responsible for septic shock but 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 evaluate the effect of intracerebroventricular (i.c.v.) administration of LPS on CIP and plasma leptin level and to investigate the involvement of sensory nerves (SN) in the effects of LPS on CIP.


METHODS
CIP was produced by subcutaneous (s.c.) infusion of caerulein (25 Kg/kg) to conscious rats. SN were deactivated with capsaicin (100 mg/kg s.c.). LPS (0.2, 2, or 20 Kg/rat) were applied to the right cerebral ventricle 30 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. Pretreatment of CIP rats with i.c.v. LPS resulted in significant reduction of CIP accompanied by dose-dependent increase in plasma levels of leptin and IL-10. Deactivation of SN, which by itself failed to affect CIP, completely reversed the beneficial effects of i.c.v. administration of LPS on CIP and reduced plasma leptin and IL-10 concentrations.


CONCLUSIONS
Pretreatment with LPS given i.c.v. prevents the development of caerulein-induced pancreatitis through the activation of SN and though the release of leptin.
Jaworek
Jolanta
J
Physiology, Collegium Medicum, Jagiellonian University Kraków, Poland.
Bonior
Joanna
J
Nawrot
Katarzyna
K
Leja
Anna
A
Sendur
Ryszard
R
Stachura
Jerzy
J
Pawlik
Wiesław
W
Konturek
Stanisław
S
D000208:Acute Disease; D017667:Adipocytes / Q000378:metabolism; D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology*; D000681:Amylases / Q000097:blood; D000818:Animals; D002211:Capsaicin / Q000633:toxicity; D002108:Ceruletide / Q000633:toxicity; D004926:Escherichia coli; D007276:Injections, Intraventricular; D016753:Interleukin-10 / Q000097:blood / Q000172:deficiency; D020738:Leptin / Q000097:blood / Q000172:deficiency / Q000502:physiology*; D008049:Lipase / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000627:therapeutic use*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013563:Sympathectomy, Chemical
D020738:Leptin; D008070:Lipopolysaccharides; D016753:Interleukin-10; D002108:Ceruletide; D008049:Lipase; D000681:Amylases; D002211:Capsaicin