Platelet-activating factor and cytokine interactions in shock

Many types of shock are characterized by profound hemodynamic alterations and depression of immune processes. Among the various mediators implicated in shock conditions, there is much evidence to suggest that, together with various cytokines, the inflammatory and chemotactic autacoid, platelet-activating factor (PAF), plays an important role. Studies on several animal models have shown that infusion of PAF mimicks the shock state, that markedly increased levels of PAF are produced in shock and that PAF antagonists afford significant protection against diverse forms of shock. The precise mechanism by which PAF antagonists protect against shock remains unclear; however, it is becoming apparent that in traumatic states a complex interaction occurs between PAF and cytokines, which leads to the acute phase reaction and circulatory collapse. We propose that PAF antagonists may be effective in counteracting shock because of their antiprotease activity and their ability to inhibit deleterious PAF/cytokine auto-generated feedback processes.