The lysis of gram-negative bacteria causes them to release lipopolysaccharide (LPS; endotoxin) from the outer membrane of their cell wall. The LPS binds to a LPS-binding protein circulating in the blood and this complex, in turn, binds to a receptor molecule (CD14) found on the surface of body defense cells called macrophages. This triggers the macrophages to release various defense regulatory chemicals called cytokines, including IL-1, IL-6, IL-8, TNF-alpha, and PAF. The cytokines then bind to cytokine receptors on target cells stimulating the production of inflammatory mediators such as prostaglandins and leukotreins as well as activating both the complement pathways and the coagulation pathway. Excessive production of clotting factors may lead to ARDS and DIC while an overproduction of prostaglandins, leukotreins, and complement proteins can damage the vascular endothelium resulting in shock and MOSF. (LPS, lipopolysaccharide; IL-1, interleukin-1; IL-6, interleukin-6; IL-8, interleukin-8, TNF-alpha, tumor necrosis factor-alpha; PAF, platelet-activating factor; ARDS, acute respiratory distress syndrome; DIC, disseminated intravascular coagulation; MOSF, multiple organ system failure.)