Early report indicated that IL-18 was upregulated in IBD patients (especially in CD), and had the pro-inflammatory effect of IL-18 by upregulating pro-inflammatory cytokines, such as TNF-α, IL-1, and IL-6 (59, 60), but these studies failed to tell whether the increased IL-18 level in patients was a consequence or causing factor for IBD. This evidence concerns the gene TNF and inflammatory bowel disease.