Interleukin-10 prevents death in lethal necrotizing pancreatitis in mice.
BACKGROUND
Cytokines derived from macrophages may play an integral role in the evolution of acute pancreatitis. Interleukin-10 (IL-10), a potent antiinflammatory cytokine, prevents the activation of macrophages and their release of inflammatory cytokines. The aim of this study was to determine whether treatment with IL-10 decreased the severity of experimental acute pancreatitis.


METHODS
Thirty female Swiss Webster mice were divided into three groups. Acute pancreatitis was induced by using a choline-deficient, 0.5% ethionine supplemented (CDE) diet. Group A (controls) received CDE diet alone. Group B was pretreated with 10,000 units of intraperitoneal IL-10 at the onset of feeding and every 8 hours thereafter. Group C received IL-10 33 hours after beginning the CDE diet and every 8 hours thereafter. One half of the animals in each group was killed at 54 hours; the remaining living animals were killed at 80 hours. Serum amylase levels (units per liter) were determined at 54 and 80 hours. Pancreata were harvested and fixed in formalin. Histologic characteristics were graded on a scale from 0 to 4 (normal to most abnormal) in a blinded fashion by two investigators.


RESULTS
Serum amylase level and histologic score (edema, inflammation, hemorrhage, and necrosis) were significantly reduced when IL-10 was administered either prophylactically or therapeutically (p < 0.01). At 54 hours all animals were alive. Mortality was reduced at 80 hours in both groups treated with IL-10 compared with those fed the CDE diet alone (p < 0.001).


CONCLUSIONS
These results suggested that macrophages play an integral role in determining the severity of acute pancreatitis in this animal model. The finding that IL-10 decreased inflammation and prevented death, even when given after acute pancreatitis was established, suggests that it may have potential for clinical use.
Kusske
A M
AM
Department of Surgery, UCLA Medical Center 90024, USA.
Rongione
A J
AJ
Ashley
S W
SW
McFadden
D W
DW
Reber
H A
HA
D000681:Amylases / Q000097:blood; D000818:Animals; D005260:Female; D016753:Interleukin-10 / Q000494:pharmacology*; D051379:Mice; D009026:Mortality; D009336:Necrosis; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*
D016753:Interleukin-10; D000681:Amylases