title: Reduction of circulating secretory phospholipase A2 levels by anti-tumor necrosis factor chimeric monoclonal antibody in patients with severe Crohn's disease. Relation between tumor necrosis factor and secretory phospholipase A2 in healthy humans and in active Crohn's disease.
abstract: BACKGROUND
  Secretory phospholipase A2 group II (sPLA2-II) has pro-inflammatory effects. The importance of tumor necrosis factor (TNF) for induction of plasma sPLA2-II in humans was studied in two groups of subjects.
  
  
  METHODS
  Six healthy volunteers received a single intravenous injection of recombinant human TNF or isotonic saline at random. Ten patients with active Crohn's disease received a single intravenous infusion of an anti-TNF chimeric monoclonal antibody, cA2.
  
  
  RESULTS
  TNF infusion in healthy volunteers resulted in an increase of sPLA2-II at 3 h, with a maximal plasma level at 6 h (20.8+/-8.9 ng/ml; P < 0.05). In Crohn's disease base-line sPLA2-II levels were 33.9+/-13.4 ng/ml 24 h after infusion of cA2, 11.0+/-2.9 ng/ml (P < 0.005). Further decrease occurred in all except two patients at 2 weeks. The decrease in plasma sPLA2-II preceded all clinical signs of remission.
  
  
  CONCLUSIONS
  TNF infusion in healthy humans can induce a rapid increase of circulating sPLA2-II, and selective blocking of TNF-alpha with cA2 results in a rapid decrease in sPLA2-II in peripheral blood. These data confirm that TNF has an important role in regulating the release of sPLA2-II in systemic and local inflammatory reactions.
authors.affiliation: Dept. of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: van Dullemen
authors.forename: G J
authors.initials: GJ
authors.lastname: Wolbink
authors.forename: P C
authors.initials: PC
authors.lastname: Wever
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
authors.forename: G N
authors.initials: GN
authors.lastname: Tytgat
authors.forename: S J
authors.initials: SJ
authors.lastname: van Deventer
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016022:Case-Control Studies; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism*; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010741:Phospholipases A / Q000096:biosynthesis / Q000097:blood* / Q000502:physiology; D054467:Phospholipases A2; D011897:Random Allocation; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D010741:Phospholipases A; D054467:Phospholipases A2