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.
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.
van Dullemen
H M
HM
Dept. of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, The Netherlands.
Wolbink
G J
GJ
Wever
P C
PC
van der Poll
T
T
Hack
C E
CE
Tytgat
G N
GN
van Deventer
S J
SJ
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*
D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D010741:Phospholipases A; D054467:Phospholipases A2