Gram negative septic shock (shock) is a major medical problem in the newborn because of its high mortality and morbibidity. TNFα is a key mediator in shock. Anti-TNFα antibodies (Abs) have been shown to have beneficial effects in shock induced by endotoxin (LPS) but not in shock induced by abdominal sepsis. Plasma endotoxin concentration increases within a short period after intraperitoneal (ip) LPS injection and declines rapidly. TNFα increases in a time-dependent manner after LPS injection. As TNFα induces TNFα gene expression, we hypothesize that Abs decrease not only plasma TNFα levels, but also TNFα gene expression, resulting in a decrease in mortality in endotoxic shock. In the present study, TNFα mRNA abundance in the liver was measured. Plasma glucose and lactate concentrations were determined.

Methods Ten day old Sprague Dawley rats were divided into 4 groups and given ip injections as follows: Group1: 0.2 ml saline;Group2: 0.1 mg/kg S. enteritidis LPS; Group3: LPS and 1 mg/kg of polyclonal Abs; Group 4: 1mg/kg of polyclonal Abs alone. Trunk blood was collected by decapitation at 0,2,4 or 8 hours after the injection, and plasma glucose and lactate concentrations were measured. Liver TNFα mRNA abundance at 2 and 8 hours was determined by Northern blot analysis. Deaths were recorded 24 hours after LPS injection.

Results In Group 2, LPS induced hypoglycemia and lactacidemia(p<0.05) and death (82%). Abs decreased the mortality (35%) in Group 3(p<0.05). Abs attenuated the hypoglycemia at 8 hours (40 ±34 and 68±13 mg/dl in Group 2 & 3, respectively). Abs also attenuated lactacidemia at 4 and 8 hours in Group 3 (p<0.05). Northern blot demonstrated a significant decrease in TNFα mRNA expression in Group 3 as compared to Group 2 (p<0.05).

Conclusion The beneficial effects of anti-TNFα antibodies on LPS induced shock are due to decreased TNFα gene expression.