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. 2006 Aug 24:4:13.
doi: 10.1186/1477-9560-4-13.

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

Sjoukje H Slofstra  1 , Hugo ten Cate, C Arnold Spek
Affiliations

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

Sjoukje H Slofstra et al. Thromb J. .

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.

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Figures

Figure 1
Figure 1
Systemic innate immune response after LPS challenge. (a) Represents the effect of low dose endotoxin priming on LPS induced IL-1β levels. (b) demonstrates KC levels, and panel (c) (d) and (e) represent respectively IL-6, IL-10 TNFα levels in plasma. (mean ± SE)
Figure 2
Figure 2
Thrombi formation in liver and lung. Formation of (micro-) thrombi after LPS challenge with and without 24 hours of low dose endotoxin priming. (a) Represents the number of thrombi in liver. (b) Demonstrates the number of thrombi in 10 microscopic fields (25×) in lung tissue. (mean ± SE)
Figure 3
Figure 3
Hepatic (ischemic) necrosis. Necrotic areas in the liver were scored for 10 microscopic fields (25×) using haematoxylin and eosin stained sections (mean ± SE)
Figure 4
Figure 4
LPS-induced kidney and liver damage. (a) Creatinine levels in plasma of mice representing kidney failure. (b+c) Transaminase leakage into plasma reflects acute cellular and mitochondrial hepatic injury (mean ± SE)
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