Interleukin 10 prevents necrosis in murine experimental acute pancreatitis.
OBJECTIVE
Inflammatory events are believed to play an important role in the pathogenesis of acute pancreatitis. Interleukin 10 (IL-10) recently emerged as a major anti-inflammatory cytokine, inhibiting the secretion of proinflammatory cytokines by monocytes and/or macrophages. The potential protective role of IL-10 in a model of acute necrotizing pancreatitis in mice was tested.


METHODS
Animals received two intraperitoneal injections of either 1000 U recombinant IL-10 or control supernatant before and during induction of acute pancreatitis with repeated cerulein injections (seven intraperitoneal injections of 50 micrograms/kg at hourly intervals).


RESULTS
Systemic amylase and lipase release peaked 9 hours after the first cerulein injection. This peak was significantly reduced by IL-10 treatment. Histologically, edema and inflammation of the pancreas were observed in both groups, whereas necrosis was dramatically reduced in IL-10-treated animals. Serum tumor necrosis factor levels were undetectable in this model; reverse-transcriptase polymerase chain reaction analysis of resected pancreatic tissues performed at the time of maximal morphological alterations showed a dramatically decreased expression of tumor necrosis factor alpha messenger RNA after IL-10 treatment compared with control pancreatitis.


CONCLUSIONS
IL-10 is able to decrease the severity of experimental acute pancreatitis, mainly by inhibiting the development of acinar necrosis. Inhibition of local tumor necrosis factor alpha might explain, at least in part, the protective effect of IL-10.
Van Laethem
J L
JL
Department of Gastroenterology, Université Libre de Bruxelles, Belgium.
Marchant
A
A
Delvaux
A
A
Goldman
M
M
Robberecht
P
P
Velu
T
T
Devière
J
J
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001483:Base Sequence; D005260:Female; D016753:Interleukin-10 / Q000627:therapeutic use*; D008049:Lipase / Q000097:blood; D051379:Mice; D008969:Molecular Sequence Data; D009336:Necrosis; D010195:Pancreatitis / Q000473:pathology / Q000628:therapy*; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D008049:Lipase; D000681:Amylases