BRIEF HYPOXIA PRECEDING E. COLI BACTEREMIA DOWNREGULATES HEPATIC TNF-α PRODUCTION / 药物分析学报

ABSTRACT

Hepatic TNF-α production following gram-negative bacteremia or hypovolemic shock predisposes to acute lung injury. However, TNF-α expression may be modified by the manner in which the hepatic O2 supply is reduced and equally important, its timing relative to bacteremia. Brief secondary hypoxic stress of buffer-perfused rat livers downregulates E. Coli (EC)-induced TNF-α expression whereas low-flow ischemia preceding EC increases subsequent TNF-α production owing to reactive O2 species (ROS). Here we determined whether 30 min of constant-flow hypoxia preceding 109 intraportal EC likewise increases antigenic and bioactive TNF-α protein concentrations during reoxygenation via production of ROS. Multiple groups (n＝38) were studied over 180 minutes, circulation antigenic TNF-α decreased in H/R+EC vs. EC controls (1 939±640 vs. 12 407±2 476 μg/L at t＝180 min; P＜0.01, along with TNF-α bioactivity). TNF-α protein were not restored to control levels in ALLO+H/R+EC. Thus, EC-induced hepatic TNF-α production and export is strongly O2-dependent in intact liver regardless of the generation of ROS or the sequence of bacteremia and modest hypoxic stress.