ABSTRACT
Human responses to gram-negative infection show a high degree of interindividual variation. The immune response to endotoxin involves a complex pattern of primary, secondary, and tertiary humoral and cellular responses. The role of the genetic background in responses to endotoxin is determined by genetic variabilities of endogenous mediators, which constitute the pathways of endotoxin-induced pathophysiology. Primary responses to endotoxin challenge are mediated by proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1. One goal in determining the role of the genetic background in responses to endotoxin is to identify genomic markers suitable for clinical use and risk stratification of patients. TNF is considered one of the important mediators of endotoxin-induced effects. Potential benefit and protection against cellular stress induced by endotoxin and its mediators is provided by intracellular heat-shock proteins. When evaluating the potential efficacy of anticytokine strategies, a clear distinction emerges between models of parenteral lipopolysaccharide or live bacterial challenge and models of focal infection.
