Modulation of natural killing by cyclo- and lipo-oxygenase inhibitors.

The effect on NK activity of two oxygenase inhibitors, indomethacin which is cyclo-oxygenase-specific at 10(-6) M and BW755C which blocks both cyclo- and lipo-oxygenase, has been analysed. The NK activity of human peripheral blood mononuclear cells (PBMC) has been studied in a 18-hr 51Cr-release assay. PBMC were incubated with the drugs for different periods of time before and during NK assay in order to analyse the correlations between the time of incubation and the modulation of NK activity. The results show that the inhibition of the cyclo-oxygenase alone, by indomethacin, enhances the NK activity if the drug is added both during and prior to the assay. In the latter case the enhancement is time dependent, reaching a maximum level after 18 hr of incubation. The simultaneous inhibition of lipo- and cyclo-oxygenase by BW755C has a rather more complex effect. The NK activity is similar to that of untreated cells after 6 hr incubation with BW755C, but is inhibited or greatly enhanced after 4 and 18 hr of incubation, respectively. These effects seem largely independent of the presence of monocytes because they can be observed with non-adherent PBMC (NA-PBMC).