Bacterial endotoxins and pathogenesis of Gram-negative infections: current status and future direction

100 years after the discovery of a bacterial 'endotoxin', 50 years after the introduction of antibiotics and 25 years after the routine use of intensive care units to support septic shock patients, Gram-negative infections continue to account for significant morbidity and mortality. In the coming decade, basic research on the structure/function of LPS, the cytokine cascade, and receptor-mediated intracellular signalling responses to LPS and cytokines will provide a greater understanding of the molecular, cellular and systemic responses to endotoxin and infection. New therapeutic agents now emerging from research, and better designed clinical trials to assess those agents will contribute to the next significant decline in sepsis- and shock-related morbidity and mortality. This article summarizes the findings of a workshop convened at the National Institutes of Health (NIH) to examine current research on endotoxin and Gram-negative septic shock.