The present study suggests that, although PAF alone induced only a minimal increase in IL-8 production, it primed the HMO proinflammatory phenotype for significant enhanced production in response to LPS. Similar patterns have been shown to apply to LPS-induced IL-1, tumor necrosis factor α, prostaglandin production by monocytes and macrophages, and superoxide production by neutrophils.13- 15,25,31 Platelet-activating factor seems to prime or reprogram the innate immune system to produce enhanced amounts of proinflammatory mediators in response to a second inflammatory stimulus. However, PAF as the sole stimulus is only a weak inducer of cytokine production. Because PAF is an autocrine and paracrine mediator produced by a variety of cells, it may act as a locoregional "alarm" for the innate immune system. In other words, production of PAF at the site of inflammation may be a means to alert the inflammatory cells in the vicinity without fully activating them. These cells are now primed or "sensitized" for enhanced production of inflammatory mediators in response to a second stimulus that otherwise would have been insufficient to trigger an inflammatory response. In this manner, even if a small amount of the offending agent, such as bacteria, is able to evade the host defense at the site of inflammation, neighboring cells such as macrophages would readily respond to amplify the host response, contain the infection, and decrease the chance of dissemination. Beneficial effects of priming are apparent as a local phenomenon. However, if generalized, and if inflammatory cells in multiple organ systems are primed, it may become harmful. In such a case, a second stimulus, which would be considered minor by the "unprimed" innate immune system, would induce an aggressive, diffuse, and nonfocused release of inflammatory mediators, and lead to MODS. In fact, results of several animal studies8- 11 using PAF and various PAF receptor antagonists suggest a role for PAF in sepsis, circulatory shock, and ischemic bowel necrosis. This role might partly be as a priming agent of the innate immune system to subsequent stimuli.