Both the onset and relief of inflammation through drug therapy (i.e., therapeutic proteins) could differentially affect levels of enzymes involved in metabolism of co-administered drugs with potential pharmacological and toxicological consequences. An In vitro model capable of propagating an inflammatory response could provide better predictive data that is more clinically relevant. This application note highlights the supplementation of the HepatoPac® platform with primary Kupffer cells in order to mimic an inflammatory environment such as cytokine production and altered CYP450 activity. Characterization of these Kupffer cell augmented co-cultures demonstrates the presence of functional Kupffer cells and metabolically competent hepatocytes. Cytokine-mediated, Kupffer cell number-dependent suppression of CYP3A4 activity and gene expression was observed supporting the use of the HepatoPac/Kupffer cell co-cultures for modeling in vivo inflammation-drug interactions.