Bacterial endotoxin induced hypothermia in pregnant rats: Role of tumor necrosis factor-a

Intraperitoneal (ip) administration of the lowest dose of Escherichia coli lipopolysaccharide (LPS) that elicits a maximal febrile response in non-pregnant rats when studied in a neutral ambient temperature (EC sub(100) - 160 kg/kg) produces a transient "regulated" hypothermia in near-term pregnant rats. The current experiments have been carried out to determine the role of tumor necrosis factor-a (TNF-a) in mediating this hypothermic response. Chronically instrumented non-pregnant and pregnant rats were housed and studied in a neutral ambient temperature and allocated to one of two experimental series depending upon whether they received ip recombinant rat TNF-a (rrTNF-a) in doses ranging from 0.1 to 1000 kg/kg or they received an antibody to tumor necrosis receptor I (TNF R1 Ab) - which neutralizes its cell surface mediated activity - before receiving an EC sub(100) dose of E. coli LPS. Intraperitoneal rrTNF-a elicited fevers in non-pregnant but not in near-term pregnant rats. In near-term pregnant rats, transient hypothermias predominated following ip rrTNF-a and occurred at doses ranging from 10 to 1000 kg / kg. As well, ip administration of TNF RI Ab eliminated the transient hypothermia following ip administration of an EC sub(100) dose of E. coli LPS in near-term pregnant rats. These data taken together provide evidence that TNF-a plays an important role in mediating the transient regulated hypothermia that occurs in near-term pregnant rats following ip administration of an EC sub(100) dose of E. coli LPS.