TUMOR-NECROSIS-FACTOR IS A MEDIATOR OF PHOSPHOLIPASE RELEASE DURING BACTEREMIA IN BABOONS

Phospholipase A (PLA) activity is elevated in plasma after polytrauma and in sepsis. During both situations, tumor necrosis factor (TNF) and free fatty acids (FFAs) are also increased. To determine whether ther e is a relationship between the changes in PLA and in TNF that occur d uring sepsis, we used a primate model of bacteremia. Live Escherichia coli (5 x 10(8) colony-forming units/kg) was injected into anesthetize d baboons (n = 10). Four of these animals were pretreated with an anti -TNF antibody (anti-TNF Ab, 15 mg/kg). After the administration of bac teria (2 h), the plasma TNF was 10.2 +/- 3.2 ng/ml. PLA and FFA reache d their maximum values of 191 +/- 14 U/I and 1.5 +/- 0.3 mM at 10 and 24 h after the injection of bacteria, respectively. In the animals tre ated with anti-TNF Ab, plasma TNF was undetectable; the highest values recorded for PLA and FFA were 71 +/- 23 U/l and 0.7 +/- 0.3 mM, respe ctively. Thus TNF appears to be an important mediator of PLA release d uring sepsis.