Graded experimental acute pancreatitis: monitoring of a renewed rabbit model focusing on the production of interleukin-8 (IL-8) and CD11b/CD18.
OBJECTIVE
To establish and monitor a rabbit model of graded severity of acute pancreatitis to test the hypothesis that interleukin-8 (IL-8) and the adhesion molecule complex CD11b/CD18 are involved in the development of systemic complications in severe acute pancreatitis.


METHODS
Acute pancreatitis induction in rabbits by duct ligation with or without infusion of 5.0% or 0.5% chenodeoxycholic acid or 0.9% saline. Control animals underwent laparotomy. The animals were monitored biochemically, histologically and immunohistochemically.


RESULTS
Increased serum levels of IL-8, tumour necrosis factor alpha (TNF-alpha), amylase and lipase were found in the chenodeoxycholic acid groups when compared with the saline, duct-ligated or control groups. Leukopenia, hypocalcaemia, and hyperglycaemia were marked in the 5.0% chenodeoxycholic acid group as compared to the saline, duct-ligated and control groups. Histologically, the 5.0% chenodeoxycholic acid group manifested a significant degree of pancreatic necrosis and neutrophil infiltration. The lungs of these animals showed acute lung injury and a significant up-regulation of CD11b/CD18. IL-8 was produced in pancreatic acinar and ductal cells. A significantly large output of ascitic fluid was seen in the 5.0% chenodeoxycholic acid group.


CONCLUSIONS
The rabbit models of acute pancreatitis are reliable in that enzymatic and histological evidence of acute pancreatitis with or without systemic complications developed. IL-8 is produced locally in pancreatic acinar and ductal cells and significantly increased in peripheral blood during severe but not mild pancreatitis. The expression of the adhesion molecule complex CD11b/CB18 is significantly increased in lung tissue during severe acute pancreatitis with acute lung injury. IL-8 and CD11b/CB18 are involved in the pathogenesis of severe acute pancreatitis but not of mild oedematous pancreatitis.
Osman
M O
MO
Department of Surgery, Arhus University Hospital, Denmark.
Lausten
S B
SB
Jakobsen
N O
NO
Kristensen
J U
JU
Deleuran
B
B
Larsen
C G
CG
Jensen
S L
SL
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001201:Ascites / Q000378:metabolism; D018845:CD11 Antigens / Q000096:biosynthesis*; D018821:CD18 Antigens / Q000096:biosynthesis*; D002635:Chenodeoxycholic Acid / Q000009:adverse effects; D002756:Cholagogues and Choleretics / Q000009:adverse effects; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000209:etiology; D006996:Hypocalcemia / Q000209:etiology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000097:blood; D007813:Laparotomy; D007970:Leukopenia / Q000209:etiology; D008026:Ligation; D008049:Lipase / Q000097:blood; D009336:Necrosis; D009504:Neutrophils / Q000473:pathology; D010179:Pancreas / Q000473:pathology; D010183:Pancreatic Ducts / Q000601:surgery; D010195:Pancreatitis / Q000097:blood / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000276:immunology; D012965:Sodium Chloride; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D015854:Up-Regulation
D018845:CD11 Antigens; D018821:CD18 Antigens; D002756:Cholagogues and Choleretics; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D002635:Chenodeoxycholic Acid; D012965:Sodium Chloride; D008049:Lipase; D000681:Amylases