EFFECT OF DEXAMETHASONE ON NF-KAPPA-B ACTIVATION, TUMOR-NECROSIS-FACTOR FORMATION, AND GLUCOSE DYSHOMEOSTASIS IN SEPTIC RATS

Glucocorticoids are potent anti-inflammatory and immunosuppressive the rapeutic agents, The protective effect of dexamethasone (DEX) on hepat ic phosphoenolpyruvate carboxykinase (PEPCK) transcript level, hepatic NF-kB (nuclear factor-kB) activation, and serum tumor necrosis factor alpha (TNF) formation was investigated in peritoneal sepsis induced b y cecal incision in rats. For the control the rats were sham-operated with laparotomies only. Each group (N = 6) was pretreated with either normal saline (NS) or DEX before surgery (NS/Sham, NS/Sepsis, DEX/Sham , and DEX/Sepsis). At 3 hr post cecal incision, DEX treatment inhibite d sepsis-induced hepatic NF-kB activation by 23%, suppressed circulati ng TNF by 50%, reduced serum glucose by 36%, reduced hepatic glycogen depletion by 76%, and attenuated PEPCK mRNA level. These findings sugg ested that DEX treatment was beneficial in attenuating glucose dyshome ostasis and significantly inhibited two sepsis-induced inflammatory me diators, NF-kB and TNF, in the early phase of peritoneal sepsis, Howev er, in the late (6 hr) septic phase, DEX treatment inhibited serum TNF by 69%, but had no effect on NF-kB activation, glycogen depletion, an d PEPCK mRNA level suggesting liver function failure injury. (C) 1997 Academic Press.