Priming of human monocytes with PAF augments their production of tumor necrosis factor.

We have recently shown that platelet-activating factor (PAF) can markedly enhance the production of tumor necrosis factor (TNF) and interleukin-1 (IL-1) by human monocytes stimulated with lipopolysaccharide or muramyl dipeptide (MDP). Because inflammatory mediators may act sequentially in vivo, we studied the effect of preexposure of monocytes to PAF on their subsequent response to cytokines in terms of TNF production. Priming monocytes for 18-48 h with graded concentrations of PAF (10(-16)-10(-6) M) markedly enhanced their subsequent TNF production in response to MDP and MDP + cytokines, by two- to three-fold. Our data suggest that priming of monocytes by PAF may be an important step in augmenting their subsequent activities in inflammatory or immune responses.