Contract Research – LPS-Induced Shock
Lipopolysaccharide (LPS) injection into mice is a model for sepsis and septic shock. Injection of high doses of LPS (300-500 µg/dose) into mice induces systemic production of cytokines, endotoxic shock, disseminated intravascular coagulation (DIC) and failure of multiple organ systems.
The sensitivity to LPS-induced lethal shock can be greatly increased by injection of D-galactosamine (D-gal). Doses of 1 µg LPS can lead to lethal shock in mice when D-gal is co-injected. D-gal sensitization enhances LPS-induced liver damage, which is characterized by hepatocyte necrosis and hemorrhage. LPS toxicity in D-gal-sensitized mice results primarily from liver injury and not from the systemic inflammatory responses.
Pretreatment of mice with α-galactosylceramide (α-GalCer) also results in higher susceptibility to LPS-induced shock, where doses of LPS as low as 1 µg can lead to lethal shock. LPS-induced shock in mice pre-treated with α-GalCer is accompanied with severe lung injury, similar to that commonly found in patients with severe sepsis.
TNF is a key mediator of LPS-induced shock and blockade of TNF protects the animals both in the high-dose LPS induced shock model and in low dose LPS-induced shock models in mice sensitized with α-GalCer or D-gal.
ICAM-1 KO mice are protected from shock induced by high doses of LPS, but not from shock induced by LPS and D-gal injection. CD137 KO mice are resistant to both high dose LPS and low dose LPS in combination with D-gal-induced lethal shock.
Bacteremia is present in septic shock but not in LPS-induced shock.
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