RELEVANCE OF PLATELET-ACTIVATING-FACTOR IN INFLAMMATION AND SEPSIS - MECHANISMS AND KINETICS OF REMOVAL IN EXTRACORPOREAL TREATMENTS

Sepsis can be considered a systemic inflammatory response syndrome (SI RS) caused by infection. When an excessive and/or persistent activatio n of humoral and cellular mechanisms of host defense is present, an ex aggerated and generalized activation of inflammatory mechanisms can le ad to a multiple organ dysfunction syndrome, Mediators thought to be i nvolved in this syndrome include the major plasma cascade systems (com plement, coagulation, and fibrinolytic systems) and soluble cell-deriv ed mediators (cytokines, reactive oxygen species, platelet-activating factor (PAF), arachidonic acid metabolites, and nitric oxide and relat ed compounds). Several findings indicate that among these mediators, P AF may exert an important role in the pathophysiology of septic shock. Evidence is accumulating that in human sepsis this scenario is far mo re complicated and that removal of inflammatory mediator excess from p lasma, rather than blockade of their potentially beneficial local prod uction, might provide a rationale for the use of continuous renal repl acement therapy (CRRT). There is an emerging view that CRRT should be considered in the light of broader concept tie, the use of blood purif ication for the treatment of sepsis), Recent studies, performed in an experimental model of continuous arteriovenous hemofiltration with exo genous PAF, demonstrated that polysulfone membranes can adsorb substan tial amounts of biologically active PAF, These studies also showed tha t the removal of this mediator occurs by a two-step process involving early adsorption followed by ultrafiltration. Although the removal of cytokines, such as tumor necrosis factor-alpha (TNF-alpha), remains co ntroversial, mainly because of differences in membrane used, operation al conditions, and inter- and intra-assay variability, the crucial poi nt is that no evidence has yet been given to show real benefit from CR RT in significantly reducing the plasma concentration of cytokines. Th e net advantage of CRRT, however, may not only be the removal of cytok ines per se, but also the simultaneous elimination of cytokine-inducin g substances. Experimental and human studies will be discussed as to w hether extracorporeal treatments may remove an excess of circulating c ytokines, either by increasing the turnover rate (the so-called high-v olume hemofiltration), or by using sorbent systems to regenerate plasm a filtrate. (C) 1997 by the National Kidney Foundation, Inc.