Induction of circulating phospholipase A2 by intravenous administration of recombinant human tumour necrosis factor

We have examined the effects of intravenous infusion of recombinant human tumour necrosis factor (rh-TNF) on serum activity of phospholipase A(2) (PLA(2)) in patients with malignancies. Nine patients received a 24 h continuous intravenous infusion ranging from 1.0 x 10(5) U/m(2) to 3.0 x 10(5) U/m(2); 14 patients received a 5 day continuous intravenous infusion ranging from 0.5 x 10(5) U/m(2)/day to 3.0 10(5) U/m(2)/day. Twenty one of 23 patients responded with marked increases in serum PLA(2) activity that were detectable 3 h after the beginning of the rh-TNF infusion and reached maximum levels at 18 h with a mean increase of 16.2-fold. In patients receiving a 5 day rh-TNF infusion, the highest levels of PLA(2) were observed after the first day of infusion. Serum PLA(2) activity declined continuously to 2.9-fold above baseline at the end of the infusion. A significant correlation was noted between the dose of infused rh-TNF and the maximum increase in PLA(2) activity. To our knowledge, this is the first time that an association between intravenous TNF administration and induction of circulating PLA(2) in man has been established.