Effects of granulocyte colony-stimulating factor on neutrophils and inflammatory cytokines in the early stage of severe acute pancreatitis in rats

Abstract

The high mortality rate of severe acute pancreatitis (SAP) is closely associated with secondary infections of pancreatic and peripancreatic tissues. It was reported that granulocyte colony-stimulating factor (G-CSF) increased the number of leukocytes and enhanced their functions. However, an inflammatory response may be enhanced by an increased number of leukocytes. Our purpose was to study the roles of G-CSF in peritoneal-exudate neutrophils and inflammatory cytokines in the early stage of experimental SAP. SAP was induced by injecting 0.2 ml of 3% taurocholate acid into the biliopancreatic duct in male Wistar rats. G-CSF (90 microg/kg body weight) or saline was administered 1 h before the SAP induction. The number of neutrophils and their phagocytic and bactericidal activities were evaluated, and the concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1beta in plasma and ascitic fluid were measured 1 h and 3 h after the SAP induction. The number of peritoneal-exudate neutrophils (PENs) at 3 h was increased by G-CSF administration (81 +/- 50 x 10(5) cells/total exudate), as compared with that shown with saline administration (28 +/- 13 x 10(5) cells/total exudate; P < 0.05). The numbers of phagocytic and bactericidal neutrophils were also elevated by G-CSF administration. G-CSF administration did not increase the concentrations of TNF-alpha, IL-6, and IL-1beta in the plasma and ascitic fluid. G-CSF increases the numbers of neutrophils and enhances their functions against bacteria, but it does not enhance intraabdominal and systemic inflammatory responses in the early stage of SAP.