THE PATHOGENESIS OF SEPSIS - FACTORS THAT MODULATE THE RESPONSE TO GRAM-NEGATIVE BACTERIAL-INFECTION

Gram-negative bacteria gain access to the bloodstream by evading host defenses. Once in circulation, lipopolysaccharide interacts with the h ost receptor CD14 and initiates the host's immune response. Lipolysacc haride stimulates the host to produce a cascade of mediators that acti vate and target leukocytes, opsonize the bacteria, and induce fever to defend against the invading bacteria. Unregulated release of these me diators, however, leads to the production of vasoactive substances, ac tivation of the clotting cascade, and diminution of cardiac performanc e, which leads to the sepsis syndrome. This article discusses the path ogenic events that lead to sepsis syndrome and reviews critical steps in regulating these inflammatory mediators to allow the host to recove r from gram-negative bacteremia.