Blockade of interleukin 6 accelerates acinar cell apoptosis and attenuates experimental acute pancreatitis in vivo
KC Chao, KF Chao, CC Chuang… - Journal of British …, 2006 - academic.oup.com
KC Chao, KF Chao, CC Chuang, SH Liu
Journal of British Surgery, 2006•academic.oup.comBackground 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 …
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 …
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.
Conclusion
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.
Oxford University Press