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 host receptor CD14 and initiates the host's immune response. Lipolysaccharide stimulates the host to produce a cascade of mediators that activate and target leukocytes, opsonize the bacteria, and induce fever to defend against the invading bacteria. Unregulated release of these mediators, however, leads to the production of vasoactive substances, activation of the clotting cascade, and diminution of cardiac performance, which leads to the sepsis syndrome. This article discusses the pathogenic events that lead to sepsis syndrome and reviews critical steps in regulating these inflammatory mediators to allow the host to recover from gram-negative bacteremia.