Inflammatory bowel disease addressed by Caco-2 and monocyte-derived macrophages: an opportunity for an in vitro drug screening assay

Abstract Inflammatory bowel disease (IBD) is a widespread disease, affecting growing demographic. The treatment of chronic inflammation located in the GI-tract dependent on severity; therefore, IBD pyramid commonly applied. Animal experimentation plays key role for novel drug development; nevertheless, it ethically questionable and limited its throughput. Reliable valid vitro assays offer opportunity to overcome these limitations. We combined Caco-2 with monocyte-derived macrophages exposed them known drugs, targeting an vitro-in vivo correlation (IVIVC) focus severity level related candidate. This co-culture assay addresses namely intestinal barrier immune response IBD. efficacy was analyzed by LPS-inflammation exposure according pyramid. Efficacy defined as range between LPS control (0%) untreated (100%) independent investigated read-out (TEER, P app , cytokine release: IL-6, IL-8, IL-10, TNF-?). release TNF-? identified appropriate readout fast screening (“yes–no response”). TEER showed remarkable IVIVC human (5-ASA, Prednisolone, 6-mercaptopurine, infliximab) R 2 0.68. Similar description adverse outcome pathway (AOP) framework, we advocate establishing “Efficacy Outcome Pathways (EOPs)” framework assays. offers easy scalable method data, which requires further validation.