Small doses of endotoxin induce in mice acute inflammatory responses similar to those occuring during the early stages of septic shock. Within hours following the administration of endotoxin, changes occur in organ functions and inflammatory cytokines & chemokines like TNF, IL6 are released.
Co administration of D-galactosamine N (GalN), results in the development of acute hepatic failure.
Blockade of TNF or TNFR1 results reduction of inflammatory responses and rescue mice from hepatic failure.
Our Preclinical Testing Tools
LPS acute sepsis (Cytokine release)
This animal model provides a unique fast screening platform for evaluation of the efficacy of anti-inflammatory drugs to counteract the responses activated following LPS exposure administration.
GaIN-LPS hepatic failure
The GalN-LPS model of hepatic failure in either wild type, hTNF transgenic mice or hTNFR1 knockin mice offers a fast and highly sensitive screening platform for the efficacy evaluation of anti-hTNF , anti-hTNFR1 therapeutics and small molecules.
Drug Efficacy Evaluation Platforms
Mice receive intraperitoneal injections of LPS alone or in combination to D-galactosamine (GalN). In the absence of treatment high proinflammatory cytokine levels are released while in the presence of GalN lethality reaches 100% within few hours. Treatment lowers cytokine levels and can eliminate lethality according to drug efficacy and dosing.
Evaluation of serum levels of cytokines and chemokines, including TNF, IL6, MCP1, CXCL1
Survival (for GaIL experiments)
ALT levels (for GaIN experiments)
Both models offer fast and highly sensitive screening platforms of anti-TNF and anti-TNFR1 therapeutics at all stages of their development. Efficacy of dozens of compounds can be screened in one day. Sensitivity is high so that even low doses of anti-TNF therapeutics offer protection.