A new screening system for nonsteroidal anti-inflammatory drugs based upon inhibition of chemiluminescence produced from human cells (granulocytes).

Abstract

A new screening system for nonsteroidal anti-inflammatory drugs that involves use of human phagocytic cells has been developed in which chemiluminescence measurement is used. Luminol-dependent chemiluminescence is measured after the addition of opsonized (coated with antibodies and complement) zymosan particles to human granulocytic leukocytes in the presence or absence of drugs. Of all the compounds tested, indomethacin was the most potent in blocking chemiluminescence, with measurable inhibitory activity at 5 mumol/L. The order of inhibitory potency at 0.1 mmol/L and in the presence of Ca2+ and Mg2+ was indomethacin greater than sodium salicylate greater than fenoprofen Ca greater than tolmetin greater than naproxen greater than ibuprofen. It is likely that the active compound itself must be added to the system because aspirin did not inhibit chemiluminescence, whereas its metabolite, sodium salicylate, was markedly inhibitory. Dexamethasone and methylprednisolone also did not inhibit chemiluminescence. The drugs that inhibit chemiluminescence are also known inhibitors of prostaglandin synthase (cyclooxygenase portion).