Platelet-activating factor (PAF-acether) enhances the concomitant production of tumour necrosis factor-alpha and interleukin-1 by subsets of human monocytes.

The production of the cytokines tumour necrosis factor (TNF) and interleukin-1 (IL-1) by human monocytes was analysed following their stimulation with muramyl dipeptide (MDP; 1 microgram/ml), in the absence or presence of graded concentrations of platelet-activating factor (PAF). Significantly enhanced production of both TNF and IL-1 was observed at two concentration ranges of PAF: a major enhancement was observed at 10(-8)-10(-6) M and this was blocked by the PAF antagonist BN 52021 (10(-4) M). A second enhancement was observed at 10(-15)-10(-14) M PAF, which was not blocked by BN 52021. Monocytes isolated either by adherence or counterflow elutriation had similar responses to PAF. The biologically inactive precursor-metabolite, lyso-PAF, had no effect on cytokine production. PAF was shown to augment the production of both bioactive TNF and IL-1 and immunoreactive TNF-alpha and IL-1 alpha and beta. Fractionation of monocytes on a discontinuous Percoll gradient yielded a denser subpopulation, which responded preferentially to higher PAF concentrations, while the less dense subpopulation responded to both concentration ranges. These data indicate that PAF can modulate monocyte functions as related to cytokine production, and may thus contribute to amplification of inflammatory reactions and regulation of immune responses by interacting with subsets of human monocytes.