What is the Innate Immunity Submodel?
The representation of the innate immune response within the model scope includes macrophage (Kupffer) and liver sinusoidal endothelial cell (LSEC) populations. Macrophages and immunomodulatory molecules produced by macrophages have been shown to modify the hepatotoxicity in animal models and patients. LSECs regulate immune cell recruitment to the liver and produce molecules that are involved in the regeneration phase in response to hepatocellular loss. Acetaminophen (APAP) serves as the primary exemplar compound as most of the available data characterizes the role of these cells and molecules in APAP hepatotoxicity. These include liposomal clodronate (for macrophage depletion), a HMGB1 antagonist, a TNF-α antagonist, and exogenous HGF.