Cytokine level changes in L-arginine-induced acute pancreatitis in rat

Acta Physiol Hung. 1996;84(2):147-56.


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.

MeSH terms

  • Acute Disease
  • Amylases / blood
  • Animals
  • Arginine
  • Biological Assay
  • Body Weight / drug effects
  • Cell Line
  • Cytokines / blood*
  • Edema
  • Hormone Antagonists / pharmacology*
  • Inflammation
  • Interleukin-6 / blood
  • Male
  • Naphthalenes / pharmacology*
  • Organ Size / drug effects
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreatitis / chemically induced
  • Pancreatitis / immunology*
  • Pancreatitis / prevention & control
  • Pentanoic Acids / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Cholecystokinin / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • Hormone Antagonists
  • Interleukin-6
  • Naphthalenes
  • Pentanoic Acids
  • Receptors, Cholecystokinin
  • Tumor Necrosis Factor-alpha
  • KSG 504
  • Arginine
  • Amylases