TNFα, an important cytokine of cell signalling, decreases gluconeogenesis in 10 day old rat hepatocytes. Sublethal endotoxin (LPS) injection in 8 day old rats causes LPS tolerance 2 days later. We hypothesize that LPS tolerance is associated with attenuated TNFα signalling.Materials and Methods Eight day old Sprague-Dawley rats receivedS.enteritidis LPS (10 μg/kg) or saline ip. Hepatocytes(106 cells/ml) were isolated 2 days later and incubated in RPMI1640 media plus [14C]-lactate with TNFα (0, 4.5×103 or 4.5×105 U/ml) for 3 hours. TNFα signalling was assessed by radiolabeled glucose production and PEPCK mRNA abundance. PEPCK mRNA was expressed as% saline+noTNFα.

Results Table

Table 1

Conclusion Sublethal LPS exposure may protect against subsequent LPS effects by down-regulation of TNFα signalling.