The Pro-Inflammatory Action of Different Pathogen-Associated Molecular Patterns in Porcine Hepatic and Intestinal...

The reduction of antibiotic use in livestock production necessitates the development of reliable in vitro models for evaluating alternative immunomodulatory compounds. In this study, porcine hepatocyte-non-parenchymal (NP) cell co-cultures and small intestinal explants exposed to pathogen-associated molecular patterns (PAMPs), including lipopolysaccharide (LPS), lipoteichoic acid (LTA), flagellin and polyinosinic-polycytidylic acid (poly I:C), were established as inflammatory models. Hepatic co-cultures exhibited pronounced inflammatory responses, with LPS and LTA increasing hepatocellular interleukin (IL)-4, IL-6, IL-8 and tumor necrosis factor (TNF)-α release, alongside elevated extracellular lactate dehydrogenase activity and maintained metabolic activity, indicating membrane perturbation without marked cytotoxicity. Poly I:C was found to be cytotoxic, accompanied by an altered cytokine profile. All PAMPs enhanced reactive oxygen species production without remarkable lipid peroxidation in most cases. In contrast, intestinal explants showed high resilience with unchanged viability and limited cytokine responses. Only IL-6 and IL-8 were detectable, with LPS elevating IL-8, while poly I:C and flagellin increased IL-6 levels. These findings demonstrate marked tissue-specific differences in inflammatory responsiveness. The hepatic co-culture model provides a sensitive system for studying robust inflammatory reactions, whereas intestinal explants are suitable for investigating moderate, gut-specific immune responses. In conclusion, these complementary models offer valuable tools for evaluating antibiotic alternatives in swine.