LPS-Induced Cytokine Release Validation Study in Mice
Charles River conducts contract studies in a validated animal model of cytokine release to test the efficacy of novel therapeutics. This model is easily modified to address client-specified study needs.
For our initial validation study, each mouse receives a lipopolysaccharide (LPS) injection. At specified time points post-LPS challenge, blood is collected for cytokine analysis (e.g., TNF, G-CSF, IL-6, IL-1B). Client studies would compare treated groups against control animals.
Rat Intravenous (IV) LPS Model
Charles River has developed a rat IV LPS-induced blood TNFα model and has profiled a number of different reference inhibitors to understand the pharmacology of the model.
We have the capability to deliver test items by multiple routes, such as oral to assess systemic action or inhaled to understand systemic contribution to the efficacy of lung-delivered compound (potentially to confirm no systemic activity for a lung-localised compound).
The primary readout for this model is TNFα inhibition, however, other cytokines could potentially be assessed. Blood can be collected for PK analysis to help build a PK/PD profile.
Note: We also offer the LPS-induced pulmonary neutrophilia model to investigate the effect of targeting mechanisms related to neutrophil recruitment and mediator release.
Figure 1: TNFα production peaks 1h following IV LPS administration (mean ± SEM)
Figure 2: Dexamethasone inhibits plasma TNFα in a dose dependent fashion. Significant inhibition of plasma TNFα observed with 15mg/kg SB239063 (p38 inhibitor) and 5mg/kg Roflumilast (PDE4 inhibitor). All reference agents dosed P.O., 2h before LPS (1h) challenge.