Analysis of Platelet-Activating Factor in Endotoxic Shock and Sepsis Using a Probability Matrix: A Critique of Meta-Analysis

This chapter examines the potential involvement of platelet-activating factor (PAF) in shock by a “probability matrix”. The production of tumor necrosis factor by human platelet-free monocytes, isolated by counterflow elutriation, was analyzed following stimulation with endotoxin in the absence or presence of graded concentration ranges of PAF. The finding of increased levels of PAF in endotoxemia suggested that PAF antagonists may be effective in counteracting this pathology. Gastrointestinal hemorrhage is feature associated with septic shock, a condition which can also be produced in several species by injection of PAF or bacterial endotoxin. The chapter investigates the mediatory role of PAF in intestinal inflammation and ulceration. Using the rat model of colitis, the effects of treatment with BN 52021 in comparison with WEB 2086 and WEB 2170 were studied in endotoxin-induced ulceration by measuring PAF biosynthesis and changes in vascular permeability.