The effects of flurbiprofen and indomethacin on the mitogenic response of human peripheral mononuclear cells

Abstract

The effects of flurbiprofen (FBP) and indomethacin (INDO) on the incorporation of [3H]thymidine into human peripheral mononuclear cells after stimulation with phytohaemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM) were investigated. FBP and INDO enhanced [3H]thymidine incorporation only at suboptimal concentrations of PHA and Con A but the concentration of PWM was less critical.Enhancement depended upon the presence of mononuclear cells which could be removed by adherence to plastic: these may be tentatively identified as monocytes (macrophages). INDO enhanced [3H]thymidine uptake to a greater degree than FBP and its effect was decreased to a greater extent by removal of monocytes.The enhancing effects of INDO and FBP are completely reversible by thorough washing of cells which had been exposed to the drugs and could be regained by direct addition of drugs to previously washed cells. Concurrent addition of both drugs to cell cultures showed neither antagonism nor synergy with respect to the effect of one drug alone. PGE2 inhibited [3H]thymidine incorporation. Like that of FBP and INDO, this action was dependent on mitogenic dose and apparent at suboptimal doses only. A low concentration of exogenous PGE2 (2 ng/ml) was sufficient to prevent the enhancing effect of both FBP and INDO.