Low dose endotoxin priming is accountable for coagulation abnormalities and organ damage observed in the Shwartzman reaction. A comparison between a single-dose endotoxemia model and a double-hit endotoxin-induced Shwartzman reaction

Abstract

Abstract The clinical response of sepsis to a systemic inflammatory infection may be complicated by disseminated intravascular coagulation or DIC. In order to experimentally study the syndrome of DIC, we aimed for a severe sepsis model complicated by disseminated coagulation. Most -simplified- experimental models describing coagulation abnormalities as a consequence of sepsis are based on single dose endotoxemia. The so called-Shwartzman reaction contrarily, is elicited by a low dose endotoxin priming followed by an LPS challenge and is characterized by pathological manifestations that represent the syndrome of DIC. In order to investigate whether the Shwartzman reaction is superior to a single endotoxin challenge as a model for sepsis-induced DIC and to determine what the pathological effect is of an encounter of low endotoxin prior to an LPS challenge, we undertook the present study. In this study we demonstrate that low-dose endotoxin priming prior to an LPS challenge in the Shwartzman reaction is accountable for micro-vascular thrombosis in lung and liver and subsequent (multi-) organ failure, not observed after a single-dose endotoxin challenge, which indicates that the Shwartzman reaction is well suited-model to study sepsis-induced DIC adversities. Remarkably, only minor differences in the innate immune response were established between the single-dose endotoxin challenge and the Shwartzman reaction.