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Endotoxin Tolerance Attenuates TNFα Signalling in 10 Day Old Rat Hepatocytes 259

TNFα decreases hepatocyte gluconeogenesis in 10 day old rats. Endotoxin injection does not induce hypoglycemia in 10 day old rats with early endotoxin tolerance. Hypoglycemia during septic shock in the newborn is primarily due to decreased gluconeogenesis. Therefore, we hypothesize that TNFα signalling is attenuated during early endotoxin tolerance. Materials and Methods Eight day old Sprague-Dawley rats received S.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 (μM/106 cells) and by Northern blot analysis for PEPCK mRNA abundance (expressed as% saline+noTNFα).Results (glucose:μM/106 cells, PEPCK mRNA:%) X±SEM, n=3-5 in each group,*p<0.05 vs Saline groups.Table