Mice receive an intraperitoneal injection of D-galactosamine and LPS. In the absence of treatment lethality reaches 100%. Treatment can reduce lethality down to 0% according to efficacy and dosing.
Even very low doses of anti-TNF therapeutics offer protection thus making the model suitable for the evaluation of therapeutics with low activity.
The model can be used for the efficacy evaluation of:
- anti-hTNF therapeutics using humanized TNF transgenic mice.
- anti-hTNFR1 therapeutics using humanized TNFR1 mice
- anti-TNF or anti-TNFR1 therapeutics recognising the mouse homolog using wt mice
Preclinical efficacy evaluation
A GalN-LPS study is completed within 72 hours. A standard protocol involves pretreatment of the animals with saline or anti-TNF therapeutic followed by GalN-LPS administration. Saline treated mice succumb within 6-10 hours while successful TNF/TNFR1 blockade delays or protects from death. Commercially available anti-hTNF therapeutics serve as positive controls of the model.
- IL-6 levels
Figure 1: Tg1278TNFKO mice were pretreated either with saline or with a range of Remicade®/Humira® doses and subsequently challenged with GalN-LPS. Low doses of Remicade® or Humira® offered protection to mice.
Figure 2: IL6 levels 2 hours after GalN-LPS administartion correlate well with the efficacy of human TNF blockade.