Model Description

Wild type or human TNF transgenic mice receive an intraperitoneal injection of LPS and blood is collected at specific time points thereafter. Pretreatment with anti-TNF agents lowers in a dose dependent manner the levels of proinflammatory cytokines and chemokines. 

Preclinical efficacy evaluation

Study design

A standard study design involves pretreatment of the experimental animal with saline or anti-TNF therapeutic followed by LPS administration and blood sampling. Serum is prepared and measured for selected cytokines & chemokines using the method of choice (ELISA, LUMINEX bioassay, CBA).  Successful anti-TNF blockade is indicated as dose dependent reduced levels of the measured cytokines & chemokines. Commercially available anti-TNF therapeutics serve as positive controls of the model. 

Read-out parameters

Evaluation of serum levels of cytokines & chemokines, including IL-6, GM-CSF & MCP-1.

Figure 1: Tg1278TNFKO mice were pretreated either with saline or with a range of Remicade doses (0.3, 1, 3 mg/kg) and subsequently challenged with LPS. Levels of serum IL-6, GM-CSF and MCP-1 were measured using the Luminex platform.