Cytokine level changes in L-arginine-induced acute pancreatitis in rat.
The role of different cytokines in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat, and the ability of KSG-504, a novel cholecystokinin receptor antagonist, to exert protection in this type of acute pancreatitis was evaluated. Male Wistar rats received 250 mg/100 g body weight of Arg intraperitoneally twice, at an interval of 1 h. Control rats received instead the same amount of glycine at the same times. Fifty mg/kg KSG-504 was injected subcutaneously 0.5 h before and 6, 18 and 36 h after the first Arg administration. Rats were examined 12, 24 and 48 h after pancreatitis induction. To assess the severity of inflammation, the edema was quantified, the serum amylase level was measured, and histologic examinations were performed. Serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels were determined by bioassay, using the TNF-sensitive WEHI 164 and the IL-6-dependent B9 cell lines, respectively. In Arg-induced acute pancreatitis, the amylase level was increased significantly at 12 h (48.600 +/- 3.980 U/l) and 24 h (30.800 +/- 3.813 U/l) vs. the control group (6.382 +/- 184 U/l). No significant alteration in the ratio pancreatic weight/body weight was found in the different groups. However, in Arg-induced acute pancreatitis, both the TNF-alpha (15.1 +/- 6.9 U/ml) and the IL-6 (39.6 +/- 19.2 pg/ml) levels were already elevated significantly at 12 h vs. the controls (3.1 +/- 0.8 U/ml and 15.2 +/- 3.1 pg/ml, respectively) and remained elevated at 24 and 48 h. Simultaneous KSG-504 administration did not modify the measured cytokine levels. No significant changes in plasma CCK levels were observed. In Arg-induced acute pancreatitis, histological evaluation revealed diffuse but microfocal necrobiotic alterations. No marked protective effects of KSG-504 were observed on histological sections. These results suggest that excessive doses of Arg induce severe acute pancreatitis in rat, with a simultaneous cytokine level elevation. Endogenous CCK does not seem to play an essential role in the pathogenesis of Arg-induced acute pancreatitis.
Takács
T
T
First Department of Medicine, Szent-Györgyi Albert Medical University, Szeged, Hungary.
Czakó
L
L
Jármay
K
K
Farkas
G
G
Mándi
Y
Y
Lonovics
J
J
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001120:Arginine; D001681:Biological Assay; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000097:blood*; D004487:Edema; D006727:Hormone Antagonists / Q000494:pharmacology*; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control; D010421:Pentanoic Acids / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D006727:Hormone Antagonists; D015850:Interleukin-6; D009281:Naphthalenes; D010421:Pentanoic Acids; D011949:Receptors, Cholecystokinin; D014409:Tumor Necrosis Factor-alpha; C085253:KSG 504; D001120:Arginine; D000681:Amylases