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

摘要

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. SUBJECTS: 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. CONCLUSION: 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.