TLR4 and Cowden disease: More relevant to CD pathogenesis, Saitoh et al. demonstrated that ATG16L1-deficient macrophages produced high amounts of the inflammatory cytokines interleukin 1-beta (IL-1β) and interleukin-18 (IL-18) following stimulation with the Toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) [69].