IMMUNE-COMPLEX MEDIATED INFLAMMATION IN THE MOUSE PERITONEAL-CAVITY - A METHOD FOR INVESTIGATING INHIBITORS OF ARACHIDONATE METABOLISM

Intraperitoneal injection of washed, preformed ovalbumin/anti-ovalbumin immune complexes caused the production of slow-reacting substance (SRS), prostaglandin E2, 6 keto prostaglandin F1a, vascular permeability (measured as extravazation of pontamine leukocyte sky blue injected previously into the blood stream), and polymorphonuclear leukocyte (PMN) infiltration in the mouse peritoneal cavity. Arachidonic acid metabolites appeared early in the response at 7.5 min; dye extravazation and PMN infiltration peaked at 30 min and 4 hr, respectively, after immune complex injection. BW755C and phenidone given orally 30 min before immune complex injection inhibited dye extravazation and SRS formation at 7.5 and 30 min. Indomethacin by the same regimen inhibited dye extravazation at 7.5 min but not at 30 min, while enhancing SRS formation at both times. Dexamethasone inhibited dye extravazation and to some extent SRS formation at both times. The data suggest that the mouse model may be useful for demonstrating an antiinflammatory activity of dual inhibitors that is clearly distinguishable from the activities shown by classical nonsteroidal antiinflammatory drugs and steroids.