title: Hyperphospholipasemia A2 in human volunteers challenged with intravenous endotoxin.
abstract: Phospholipase A2 (PLA2) activity was measured in the serum of 23 individuals infused intravenously with endotoxin (EN) at a dose of 4 ng/kg body weight. A marked increase in PLA2 was noted 3 h after EN challenge (mean 828 +/- 513 units/ml), reached its maximum at 24 h after the challenge (mean 2667 +/- 2442 units/ml), and was still evident at 48 h (mean 763 +/- 366 units/ml). In contrast, TNF levels were maximal (mean 712 +/- 375 pg/ml) 90 min after the EN challenge and subsided to very low values (5 +/- 5 pg/ml) 5 h after the challenge. There was a positive correlation between the maximum response of TNF and that of PLA2 (r = 0.82, P < 0.01). Administration of ibuprofen or pentoxifylline did not alter the PLA2 response. EN challenge did not affect serum pancreatic PLA2 concentration or that of the lysosomal cationic enzyme, lysozyme. Neutralizing antibody against human recombinant (synovial type) PLA2 completely abolished PLA2 activity in the sera tested. We conclude that EN infusions cause marked intravascular release of nonpancreatic secretory PLA2 and that the magnitude of this response seems to be related to the prior generation of TNF.
authors.affiliation: Inflammation Research Group, University of Toronto, Ontario, Canada.
authors.forename: W
authors.initials: W
authors.lastname: Pruzanski
authors.forename: D W
authors.initials: DW
authors.lastname: Wilmore
authors.forename: A
authors.initials: A
authors.lastname: Suffredini
authors.forename: G D
authors.initials: GD
authors.lastname: Martich
authors.forename: A G
authors.initials: AG
authors.lastname: Hoffman
authors.forename: J L
authors.initials: JL
authors.lastname: Browning
authors.forename: E
authors.initials: E
authors.lastname: Stefanski
authors.forename: B
authors.initials: B
authors.lastname: Sternby
authors.forename: P
authors.initials: P
authors.lastname: Vadas
mesh_terms: D004731:Endotoxins / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D010741:Phospholipases A / Q000097:blood*; D054467:Phospholipases A2; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D010741:Phospholipases A; D054467:Phospholipases A2