Additional inhibitors of rat serum acute phase alpha 2-macroglobulin levels. Effect of 6-mercaptopurine and some lipoxygenase and cyclo-oxygenase inhibitors.

With the use of a previously described electroimmunoassay, 4 more compounds were found to depress acute phase alpha 2-macroglobulin levels in rat serum following the injection of turpentine. The compounds, meclofenamic acid, dextropropoxyphene, 5,8,11,14-eicosatetraynoic acid and 6-mercaptopurine are thus grouped with a variety of anti-inflammatory agents, cyclo-oxygenase inhibitors, hypolipidaemics and colchicine, all of which share the property of reducing the concentration of alpha 2-macroglobulin in rat serum. Compounds with immunosuppressant properties, namely amethopterin, azathioprine, cyclophosphamide and 5-fluorouracil, the steroids, betamethasone and dexamethasone, the lipoxygenase inhibitor, nordihydroguaiaretic acid, and MK477, a compound said to stimulate prostaglandin synthesis, did not reduce serum levels of the acute phase protein. 6-Mercaptopurine, a compound known to show anti-inflammatory properties in some systems, proved to be the strongest inhibitor found so far. The rat acute phase protein electroimmunoassay may thus be an effective screen for detecting a new class of anti-inflammatory agents. Knowledge of the mechanisms of action of drugs that depress rat serum alpha 2-macroglobulin concentrations may promote understanding of the control of acute phase protein production by the liver.