Taking into consideration the upregulatory effects of TNF-α on the sensitivity of the HIF pathway and its regulatory components in inflamed tissues, in theory, inhibition of TNF-α in patients with IBD can lead to downregulation of HIF-1α and its consequent protective effects on barrier function, thus suggesting a potential reason for unresponsiveness of a large number of patients to such therapy. This evidence concerns the gene TNF and inflammatory bowel disease.