The effect of non-steroidal anti-inflammatory drugs on phytohaemagglutinin stimulated lymphocytes: relevance to possible therapeutic immunosuppression by fenclofenac.

Representatives of seven chemical groups of non-steroidal anti-inflammatory drugs were tested for their effect on activation and replicative growth of phytohaemagglutinin stimulated normal human lymphocytes in vitro at concentrations in the high therapeutic range, and, where possible, at 10 times that concentration. Fenclofenac was noted to be suppressive. Fenclofenac and diclofenac (the only available phenylacetic acid derivatives) were studied in more detail. The two drugs were equipotent in vitro. At low concentrations they enhanced replicative growth, due to cyclo-oxygenase inhibition of cells from some subjects, but at higher concentration they suppressed replicative growth of cells from all subjects, with only a minor effect on activation at very high concentration. However, the potency for clinical effect of fenclofenac and diclofenac is very different, because fenclofenac at therapeutic blood concentrations suppressed replicative growth in vitro, whereas therapeutic concentrations of diclofenac were inactive in lymphocyte suppression. It is suggested that the phenylacetic acid derivative non-steroidal anti-inflammatory drugs may have a composite action in vivo: by inhibition of cyclo-oxygenase they reduce prostaglandin production (and so produce some symptomatic relief in the same manner as the drugs in the other chemical groups of non-steroidal anti-inflammatory agents) and by suppression of lymphocyte replication they may interfere with the pathogenesis of certain chronic rheumatic diseases.