Figure 7.

Proposed schema for progression of the endotoxic response. LPS, released by gram negative bacteria, interacts with inflammatory cells leading to generation of TNF-α and other cytokines. TNF-α, acting upon endothelium, stimulates sphingomyelin hydrolysis to ceramide via an ASMase. Apoptosis of the endothelium ensues, which can be blocked by bFGF via inhibition of ceramide generation. We further propose that endothelial apoptosis results in generalized microvascular dysfunction sufficient to compromise the circulation to major organs, leading to nonendothelial tissue damage, circulatory collapse, and death.