IGF-1 stimulates production of interleukin-10 and inhibits development of caerulein-induced pancreatitis.
OBJECTIVE
Insulin-like growth factor-1 (IGF-1) and other growth factors overexpression was reported in acute pancreatitis. Previous studies have shown the protective effect of epidermal growth factor (EGF), Hepatocyte Growth Factor (HGF) and Fibroblast Growth Factor (FGF) in the course of experimental acute pancreatitis. The aim of our studies was to determine the effect of IGF-1 administration on the development of caerulein-induced pancreatitis.


METHODS
Acute pancreatitis was induced by infusion of caerulein (10 micro/kg/h) for 5 h. IGF-1 was administrated twice at the doses: 2, 10, 50, or 100 micro/kg s.c.


RESULTS
Administration of IGF-1 without induction of pancreatitis increased plasma interleukin-10 (IL-10). Infusion of caerulein led to development of acute edematous pancreatitis. Histological examination showed pancreatic edema, leukocyte infiltration and vacuolization of acinar cells. Also, acute pancreatitis led to an increase in plasma lipase and interleukin 1beta (IL-1beta) level, whereas pancreatic DNA synthesis and pancreatic blood flow were decreased. Treatment with IGF-1, during induction of pancreatitis, increased plasma IL-10 and attenuated the pancreatic damage, what was manifested by histological improvement of pancreatic integrity, the partial reversion of the drop in pancreatic DNA synthesis and pancreatic blood flow, and the reduction in pancreatitis-evoked increase in plasma amylase, lipase and IL-1beta level. Protective effect of IGF-1 administration was dose-dependent. Similar strong protective effect was observed after IGF-1 at the dose 2 x 50 and 2 x 100 microg/kg.


CONCLUSIONS
(1) Administration of IGF-1 attenuates pancreatic damage in caerulein-induced pancreatitis; (2) This effect is related, at least in part, to the increase in IL-10 production, the reduction in liberation of IL-1beta and the improvement of pancreatic blood flow.
Warzecha
Z
Z
Department of Physiology, Jagiellonian University Medical School, Kraków, Poland. mpdembin@cyf-kr.edu.pl
Dembinski
A
A
Ceranowicz
P
P
Konturek
S J
SJ
Tomaszewska
R
R
Stachura
J
J
Konturek
P C
PC
D000818:Animals; D002108:Ceruletide / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D004247:DNA / Q000009:adverse effects / Q000096:biosynthesis / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000097:blood / Q000494:pharmacology; D008049:Lipase / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000502:physiology; D008297:Male; D010179:Pancreas / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology; D010195:Pancreatitis / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014617:Vacuoles / Q000187:drug effects / Q000473:pathology
D007375:Interleukin-1; D016753:Interleukin-10; D007334:Insulin-Like Growth Factor I; D002108:Ceruletide; D004247:DNA; D008049:Lipase