Attenuated febrile response to lipopolysaccharide in rats with biliary obstruction.

Abstract

Patients with biliary tract obstruction have unexplained, inordinately high rates of perioperative morbidity and mortality, whereas cholestatic animals display abnormal hypothalamic responses to pyrogenic stimuli. We asked if obstructive cholestasis was associated with abnormal fever generation. Male Sprague-Dawley rats (250 g) underwent laparotomy for implantation of thermistors and either bile duct resection (BDR) or sham operation. After recovery, temperatures were recorded by telemetry and conscious, unrestrained rats in each group were injected intraperitoneally with either interleukin-1beta (IL-1beta;1 microg/kg) or Escherichia coli lipopolysaccharide (LPS; 50 microg/kg). Baseline temperatures in both groups were similar. Febrile responses after IL-1beta injection in BDR and sham groups were not significantly different. However, in response to LPS injection, BDR rats showed an initial hypothermia with a subsequently attenuated febrile response. Administration of anti-tumor necrosis factor-alpha (TNF-alpha) antibody 2 h before LPS injection blocked the LPS-induced hypothermia seen in BDR animals. However, 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).