Platelet-activating factor in septic shock.
Septic shock induced by endotoxins of Gram-negative bacteria, or toxins of Gram-positive bacteria and fungi, deserves particular interest because of its high mortality rate. In experimental animals, treatment with bacterial lipopolysaccharide (endotoxin of Gram-negative bacteria) mimics the symptoms of septic shock. Thus, this treatment has become an important method in animal models of septic shock. Endotoxin induces release of platelet-activating factor and cytokines, such as tumor necrosis factor and interleukins. Platelet-activating factor derived from macrophages, polymorphonuclear leukocytes, and platelets is a potent phospholipid inflammatory mediator that increases cell adhesion and activates endothelial cells by direct effect or through formation of toxic oxygen species and arachidonic acid metabolites, such as thromboxane A2 and leukotriene B4. Platelet-activating factor interacts with cytokines, and this interaction leads to an autocatalytic amplification of inflammatory mediator release. The release of inflammatory mediators by interaction of platelet-activating factor with cytokines is characterized by bell-shaped concentration-effect curves. For example, in a certain concentration range, platelet-activating factor or cytokines induce a mediator release that is proportional to the stimulation. However, over-stimulation may lead to a decrease of mediator release or a prevalence of the release of a single mediator. Down-regulatory processes may be brought about by platelet-activating factor-induced prostacyclin or adenosine release that activates adenylate cyclase and increases intracellular cyclic adenosine 3'5'-monophosphate concentrations. Down-regulation may protect inflammatory and endothelial cells from overstimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Koltai
M
M
Institut Henri Beaufour, Le Plessis Robinson, France.
Hosford
D
D
Braquet
P G
PG
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D012772:Shock, Septic / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*
D010972:Platelet Activating Factor