The Role of TNF in the Pathogenesis of Inflammatory Bowel Disease

Abstract

Tumor necrosis factor (TNF) is a pleotropic cytokine involved in a wide range of pathological processes, including inflammatory bowel disease (IBD). In the past, TNF was recognized as a pro-inflammatory cytokine with deleterious effects. This has led to the development of anti-TNF drugs, which revolutionized the treatment of inflammatory disorders such as Crohn's disease. However, in the past 20 years, clinical studies have shown that anti-TNF drugs are not always effective. Moreover, in some rare cases, anti-TNF drugs can even cause an aggravation of the disease. Nowadays, there is increasing evidence that TNF is not only detrimental but can also play an important role in health and the maintenance of homeostasis. The aim of this chapter is to briefly summarize the literature demonstrating the complex dichotomous role of TNF in IBD and discuss the role of anti-TNF drugs in the treatment of IBD.

Probiotic Lactobacillus and Bifidobacterium Strains Counteract Adherent-Invasive Escherichia coli (AIEC) Virulence and Hamper IL-23/Th17 Axis in Ulcerative Colitis, but Not in Crohn’s Disease

“…Another key player in intestinal inflammation during IBD is the cytokine TNF-α [61]. Indeed, very high TNF-α levels are present in the gut mucosa of IBD patients and positively correlate with clinical disease severity, thus suggesting a negative contribution for TNF-α to the chronic intestinal inflammation.…”

Translating Treg Therapy for Inflammatory Bowel Disease in Humanized Mice

“…And, it put on more on risk during the combinational therapy [122]. Other than this other paradoxical side effects such as psoriasis/psoriasiform skin, development of sarcoidosis-like lesions, late occurrence of arthritis/synovitis and lupus-like syndrome (0.5 to 1% of patients) can also be developed [123][124][125][126][127]. Additionally, novel therapies including JAK inhibitor [128][129][130], anti-MAdCAM-1 [131][132][133][134][135], an anti-SMAD7 antisense oligonucleotide (mongersen) [136][137][138], S1P1 [128,139] and anti-interleukin (IL)-12/23 (ustekinumab) [140][141][142][143][144][145][146] have been under investigation for safety and other purposes.…”

Detection of Unspecified Inflammatory Bowel Disease, Crohn’s Disease and Ulcerative Colitis via Metabolite Analysis and Machine Learning

“…APP has shown strong links to Alzheimer's disease, but research also suggests that APP may influence susceptibility towards gut inflammatory diseases [61]. Evidence showing a link between TNF and IBD have been reported in previous publications in which IBD-patients showed increased levels of TNF in their serum samples [62]. Additionally, the metabolites-cyclic AMP and nitric oxide-appear to be a major contributor to many sub-networks in this third network, with direct links to both APP and TNF.…”

“…5h) includes metabolites that interact with TNF and MYC protein complexes. Previous findings suggest that IBD-patients show increased levels of TNF in their serum samples [62]. As for the effect of MYC in CD, it has been found that in active CDpatients, the down-expression of c-MYC in patients' epithelium may result in attenuated cell proliferation, which therefore suggest that it could contribute to mucosal ulceration [69].…”