INFLAMMATORY MEDIATORS AND THEIR INFLUENCE AN HEMOSTASIS

Sepsis is the most important cause of mortality in the Intensive Care Units. At present, sepsis is understood to be the inflammatory respons e of the host to infection, rather than a direct effect of microbial a ggression. From the clinical standpoint, this inflammatory response is known as systemic inflammatory response syndrome (SIRS). Pathophysiol ogically, SIRS is characterized by the activation of several groups of cell (monocytes/macrophages, PMNs, and endothelial cells) and by the release of inflammatory mediators (cytokines and others). Tumor necros is factor (TNF) is the first cytokine released by endotoxin action ove r monocyte/macrophage. TNF secretion, modulated by interferon gamma (I FN gamma) and interleukin 10 (IL-10), is followed by release of other cytokines such as interleukins (IL) (IL-1, IL-6 and IL-8). These media tors are able to act over hemostasis activating the extrinsic pathway through tissue factor expression. The action of the mediators over end othelial cells induces an increase in plasminogen activator inhibitor type 1 (PAI-1) levels with inhibition of fibrinolysis. Both coagulatio n activation and fibrinolysis blockage result in fibrin deposit in the microvascular system. The complexity of the mechanisms implicated in systemic inflammatory response make a general rule so difficult to est ablish, because patient response is highly individualized and it is no t possible to know which moment of this dynamic process is being analy zed.