Interleukin-6 (IL-6) exerts a wide spectrum of regulatory activities during immune and inflammatory responses. The aim of this study was to investigate the role of endogenous
IL-6 in the inflammatory response associated with
acute pancreatitis.
Acute pancreatitis was induced by hourly (x5) i.p.
injections of
cerulein (50 microg/kg, suspended in
saline solution) in
IL-6 deficient mice (IL-6-KO) and wild-type (IL-6WT) littermates. IL-6KO mice exhibited a more severe tissue injury and a higher rate of mortality and when compared to IL-6WT mice.
Acute pancreatitis was characterized by
edema, neutrophil infiltration, tissue
hemorrhage and cell
necrosis, upregulation of
P-selectin and
intercellular adhesion molecule-1 (ICAM-1), as well as increases in the serum levels of
amylase and
lipase. The degree of oxidative and nitrosative tissue damage was significantly greater in IL-6KO mice than in wild-type littermates, as indicated by higher tissue levels of
malondialdehyde and nitrosylated
proteins. Plasma levels of the inflammatory
cytokines tumour
necrosis factor-alpha and
interleukin-1beta were also greatly enhanced in IL-6KO mice when compared to wild-type mice. These events were correlated with 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 in IL-6KO mice subjected to
acute pancreatitis than in the corresponding WT mice. These data demonstrate that endogenous
IL-6 exerts an anti-inflammatory role during
acute pancreatitis, possibly by regulating the expression of adhesion molecules, the subsequent adhesion and activation of neutrophils and finally the generation of
cytokine and reactive
oxygen or
nitrogen species.