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

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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-α (TNF-α) 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-α (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.

Original languageEnglish
Pages (from-to)147-156
Number of pages10
JournalActa physiologica Hungarica
Volume84
Issue number2
Publication statusPublished - Dec 1 1996

Keywords

  • Interleukin-6
  • KSG-504
  • L-arginine-induced acute pancreatitis
  • Plasma cholecystokinin level
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology (medical)

Fingerprint Dive into the research topics of 'Cytokine level changes in L-arginine-induced acute pancreatitis in rat'. Together they form a unique fingerprint.

  • Cite this