LIPOPOLYSACCHARIDE SIGNAL-TRANSDUCTION, REGULATION OF TUMOR-NECROSIS-FACTOR BIOSYNTHESIS, AND SIGNALING BY TUMOR-NECROSIS-FACTOR ITSELF

In recent years, the chain of events that connects introduction of bac terial endotoxin (lipopolysaccharide; LPS) into a mammalian host, and the syndrome of organ damage and vascular collapse that ensues, have c ome into sharper focus. Several of the molecules that engage LPS, and a rough outline of the signaling cascade that leads to cytokine releas e from mononuclear cells, have been elucidated. The principal cytokine s that mediate the untoward effects of LPS have also been identified. The most important of these is tumor necrosis factor (TNF), which elic its biologic responses from virtually every type of cell to which it b inds. Two distinct receptors transduce the TNF signal. Mechanisms of T NF receptor action are becoming increasing clear, and there is reason to hope that, through intervention at many distinct levels, the devast ating effects of LPS might be attenuated or averted.