There are many potential mechanisms by which patients with IBD may fail to respond to anti-TNF therapy, including activation of alternative inflammatory pathways, neutralizing antibodies, subtherapeutic levels, or inability to block autocrine IEC-derived TNF, but it is tempting to consider whether LTα3-mediated TNFR1-induced IEC death could play a role in a subset of patients. This evidence concerns the gene TNF and inflammatory bowel disease.