TNF and Crohn ileitis: In addition, the possibility exists that during chronic, established ileitis, the effects of probiotics, and induced epithelial TNF, are not effective due to either the presence of copious amounts of macrophage-derived TNF, different TNFR-bearing effector cell populations during later, chronic phases of intestinal inflammation, or actual downregulation of TNFRs, likely as a negative feedback mechanism in response to increasing local levels of TNF.