Effects of glucocorticoid agonist and antagonist on the pathogenesis of L-arginine-induced acute pancreatitis in rat.
OBJECTIVE
To investigate the consequences of treatment with an exogenous glucocorticoid agonist (methylprednisolone) and antagonist (RU-38486) on the local and systemic responses in L-arginine-induced acute pancreatitis in rats.


METHODS
The methylprednisolone and RU-38486 were administered just before pancreatitis induction. Plasma amylase activity, interleukin 6 activity, pancreatic weight/body weight ratio, plasma macrophage migration inhibitory factor (MIF) concentration, and pancreatic nuclear transcription factor (NF) kappaB activity were determined. The extents of pancreas, liver, and lung injuries were assessed by histology.


RESULTS
Acute pancreatitis resulted in NF-kappaB activation and proinflammatory cytokine release in rats. In the glucocorticoid agonist group, plasma amylase and interleukin 6 levels were significantly decreased as compared with those of RU-38486 and nontreated groups. Antagonist treatment led to significantly higher MIF production at 8 and 12 hours after L-arginine injection as compared with the agonist-treated and nontreated groups. Glucocorticoid agonist treatment significantly decreased the level of NF-kappaB 24 hours after pancreatitis induction. Histological investigations showed protective effect of agonist treatment on acute pancreatitis-induced tissue damage in the pancreas and lung.


CONCLUSIONS
These results corroborated the importance of MIF in acute pancreatitis. The glucocorticoid-dependent mechanisms seem to play a crucial role in the control of the inflammatory response and tissue damage in L-arginine-induced experimental acute pancreatitis.
Paszt
Attila
A
Department of Surgery, University of Szeged, Szeged, Hungary. paszt@freemail.hu
Eder
Katalin
K
Szabolcs
Annamária
A
Tiszlavicz
László
L
Lázár
György
G
Duda
Ernö
E
Takács
Tamás
T
Lázár
György
G
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001120:Arginine / Q000633:toxicity; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D007739:L Cells; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D051379:Mice; D015735:Mifepristone / Q000627:therapeutic use*; D010195:Pancreatitis / Q000139:chemically induced* / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar
D005938:Glucocorticoids; D015850:Interleukin-6; D008263:Macrophage Migration-Inhibitory Factors; D015735:Mifepristone; D001120:Arginine; D000681:Amylases; D008775:Methylprednisolone