Sepsis


Clinical Background

Sepsis is a life threatening condition in which the body has a severe reaction to bacteria or other infection. The response is referred to as systemic inflammatory response syndrome (SIRS). It involves a widespread inflammatory condition in which blood pressure decreases causing several organs to cease functioning due to a lack of blood flow. Treatment options are currently limited and include antibiotics, oxygen support, fluids, and medications to increase blood pressure.

Preclinical Models

Model Description Length Endpoints
Acute Sepsis
LPS administration resulting in elevated cytokines 4 hours Cytokine levels
Survival Sepsis
The LD50, LD75, or LD100 dose of LPS is administered and survival examined 5 – 7 Days Survival, Weight change

 

Acute Sepsis

A hallmark of sepsis is the widespread elevation of cytokines. In rodents, lipopolysaccharide (LPS) elicits a strong immune response within hours following administration. In the acute model, this response is measured by examining IL-6, TNF-α, or other cytokine concentrations in blood serum. Compounds which prevent the elevation of cytokines are predicted to be efficacious for sepsis.

Serum IL-6

 

Serum TNF – a

 

Survival Sepsis

In severe cases, sepsis can be a life threatening condition. To model severe sepsis in rodents, LPS is administered at doses expected to produce 50%, 75%, or 100% mortality within 5 days of administration. Potentially lifesaving treatments are examined by measuring the effect of treatment on increasing percent survival.

Survival