Attenuated febrile response to lipopolysaccharide in rats with biliary obstruction

Patients with biliary tract obstruction have unexplained, inordinately high rates of perioperative morbidity and mortality, whereas cholestatic animal s display abnormal hypothalamic responses to pyrogenic stimuli. We asked if obstructive cholestasis was associated with abnormal fever generation. Mal e Sprague-Dawley rats (250 g) underwent laparotomy for implantation of ther mistors and either bile duct resection (BDR) or sham operation. After recov ery, temperatures were recorded by telemetry and conscious, unrestrained ra ts in each group were injected intraperitoneally with either interleukin-1 beta (IL-1 beta; 1 mu g/kg) or Escherichia coli lipopolysaccharide (LPS; 50 mu g/kg). Baseline temperatures in both groups were similar. Febrile respo nses after IL-1 beta injection in BDR and sham groups were not significantl y different. However, in response to LPS injection, BDR rats showed an init ial hypothermia with a subsequently attenuated febrile response. Administra tion of anti-tumor necrosis factor-alpha (TNF-alpha) antibody 2 h before LP S injection blocked the LPS-induced hypothermia seen in BDR animals. Howeve r, serum levels of TNF-alpha were not significantly different between sham and BDR animals after LPS injection at any time point measured (0, 1.5, and 3 h).