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.

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

Dugo L;
2002-01-01

Abstract

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12610/3073
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