TLR4 and inflammatory response: In Crohn’s disease, intestinal inflammation is believed to result from a complex interplay between environmental factors and a dysregulated innate immune system in a genetically predisposed individual.39 Macrophages and monocytes at inflamed intestinal sites are potential sources for the extracellular secretion of DAMPs such as HMGB1, where dsHMGB1 and frHMGB1 may act by binding to TLR4 and RAGE receptors, respectively.40