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

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.Severe bacterial infections may pass into the bloodstream where endotoxin or lipopolysaccharide (LPS) present on the outer membranes of (gram-negative) bacteria can provoke a systemic inflammatory response syndrome. The term sepsis is used to identify the continuum of the clinical response to such a systemic infection and sepsis may progress to severe sepsis or septic shock when additional organ dysfunction and hypoperfusion develop [1]. The initial manifestation of the infection is overwhelming inflammation, known as the innate immune response.Furthermore, severe sepsis is complicated by disseminated intravascular coagulation (DIC), a syndrome characterized by micro-vascular thrombosis and (multi-) organ failure consequently increasing mortality rate [2]. Although a contributory relation between intravascular deposition of fibrin, as a result of the systemic activation of coagulation, and the development of organ damage is not firmly established, anticoagulant strategies are believed to benefit the condition of DIC [2,3]. Thus far, the restoration of the anti-coagulant protein C pathway by the infusion of recombinant human activated protein C (APC) is the only treatment strategy proven to improve sepsis-related mortality [4]. Interestingly, sub-group analysis indicated that patients who were classified as having DIC, (according to the DIC scoring system of the ISTH [5]) had a relatively greater benefit of APC treatment than patients who did not