Absence of endogenous interleukin-6 enhances the inflammatory response during acute pancreatitis induced by cerulein in mice

Interleukin-6 (IL-6) exerts a wide spectrum of regulatory activities during immune andinflammatory responses. The aim of this study was to investigate the role of endogenous IL-6 inthe inflammatory response associated with acute pancreatitis. Acute pancreatitis was induced byhourly (5) i.p. injections of cerulein (50 g/kg, suspended in saline solution) in IL-6 deficientmice (IL-6–KO) and wild-type (IL-6WT) littermates. IL-6KO mice exhibited a more severetissue injury and a higher rate of mortality and when compared to IL-6WT mice. Acutepancreatitis was characterized by edema, neutrophil infiltration, tissue hemorrhage and cellnecrosis, upregulation of P-selectin and intercellular adhesion molecule-1 (ICAM-1), as well asincreases in the serum levels of amylase and lipase. The degree of oxidative and nitrosative tissuedamage was significantly greater in IL-6KO mice than in wild-type littermates, as indicatedby higher tissue levels of malondialdehyde and nitrosylated proteins. Plasma levels of theinflammatory cytokines tumour necrosis factor- and interleukin-1 were also greatlyenhanced in IL-6KO mice when compared to wild-type mice. These events were correlatedwith an increase in the staining (immunoreactivity) for poly (ADP-ribose) polymerase (PARP)in the pancreas of cerulein-treated IL-6WT. The staining for PARP was more pronounced inIL-6KO mice subjected to acute pancreatitis than in the corresponding WT mice. These datademonstrate that endogenous IL-6 exerts an anti-inflammatory role during acute pancreatitis,possibly by regulating the expression of adhesion molecules, the subsequent adhesion andactivation of neutrophils and finally the generation of cytokine and reactive oxygen or nitrogenspecies.