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. 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.