Blockade of interleukin 6 accelerates acinar cell apoptosis and attenuates experimental acute pancreatitis in vivo.
BACKGROUND
It remains unclear whether interleukin (IL) 6 plays a role in initiating either the inflammatory or antiapoptotic responses in severe acute pancreatitis. This study examined the effect of neutralizing antibody against IL-6 on the induction of pancreatic acinar cell apoptosis and attenuation of the severity of severe acute pancreatitis.


METHODS
Experiments were conducted on laboratory mice with severe acute pancreatitis induced by lipopolysaccharide injection following six injections of caerulein at intervals of 6 h. Neutralizing monoclonal anti-IL-6 antibody was administered either 5 min or 2 h after the first caerulein injection. Apoptosis in pancreatic sections was determined by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labelling method.


RESULTS
Administration of caerulein and LPS induced an increase in serum amylase and IL-6 levels, severe acute pancreatitis, pancreatitis-associated lung injury, and phosphorylation of signal transducer and activator of transcription (STAT) 3 in the pancreas. A neutralizing antibody against IL-6 effectively suppressed these responses. Application of IL-6 neutralizing antibody caused the induction of apoptosis in the pancreatic acinar cells of mice with acute pancreatitis.


CONCLUSIONS
Blocking IL-6 suppresses STAT-3 activation in the pancreas and consequently attenuates the severity of severe acute pancreatitis by promotion of pancreatic acinar cell apoptosis.
Chao
K C
KC
Institute of Toxicology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei, 10043, Taiwan.
Chao
K F
KF
Chuang
C C
CC
Liu
S H
SH
D000681:Amylases / Q000097:blood; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002108:Ceruletide / Q000008:administration & dosage; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010195:Pancreatitis / Q000097:blood / Q000473:pathology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors; D000093242:Interleukin-6 Inhibitors
D000681:Amylases; D002108:Ceruletide; D015850:Interleukin-6; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor; D000093242:Interleukin-6 Inhibitors