Tumor Necrosis Factor’s Pathway in Crohn’s Disease: Potential for Intervention

Abstract

Crohn’s disease (CD) is a chronic disorder characterized by full thickness patchy inflammation of the gastrointestinal tract. The pathogenesis is multifactorial and involves defective innate immune responses, microbiome alterations, and dysregulated activation of the acquired component of mucosal immunity. One of the molecular mediators that is involved at different levels in the initiation and progression of intestinal inflammation characteristic of CD is tumor necrosis factor (TNF). The present manuscript provides a comprehensive review focused on the potential role of TNF in the different phases of CD pathogenesis, particularly in light of its potential clinical implications. Currently available drugs blocking TNF are evaluated and discussed, specifically for open issues that still remain utilizing such therapy. TNF exerts a paramount role in the established phase of intestinal inflammation that characterizes CD patients, and anti-TNF biologics have definitely changed patient management, offering effective and safe options of treatment. Nonetheless, many patients still do not respond to anti-TNF therapy or experience unwanted side-effects. This could partially be due to the role that TNF plays in intestinal homeostasis that is particularly important during the early phase of the inflammatory process. In fact, emerging evidence supporting the dichotomous role of TNF and the identification of molecular markers will guide a more tailored and refined therapy for CD patients in the near future.

Establishment of Epithelial Inflammatory Injury Model Using Intestinal Organoid Cultures

“…As we know, TNF-α is produced by the monocytic lineage and plays an important role in both homeostatic and pathological conditions [20]. Previous studies have shown that patients with chronic intestinal inflammation show elevated TNF-α level due to elevated numbers of TNF-α-secreting cells in the intestine [21,22]. Besides immune cells, Paneth cells also constitutively produce TNF-α in mice as well as in patients suffering from chronic intestinal inflammation [23].…”

Acute Neurological Involvement after Donor Lymphocyte Infusion for Post-Transplant Viral Infection: The Same Pattern of Novel Cancer Immunotherapy-Related CNS Toxicity?

“…Given its crucial role in the inflammatory process, this molecule has been the therapeutic target of specific pharmacological treatments, the most significant example of which is infliximab, the use of which is approved for pathologies such as rheumatoid arthritis and chronic inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) [ 29 , 30 , 31 ].…”

Microbiota and Gut Health: Promising Prospects for Clinical Trials from Bench to Bedside

“…These two transcription factors involve in many inflammation encoded gene. As a result, induce inflammation at colon sites (i) Pagnini and Cominelli, [56] (ii) Schmitt, Neurath and Atreya, [57] Th1 cell, intestine epithelial cells, Treg (i) Inhibits both antigen presentation and subsequent proinflammatory cytokine release, resulting an unbalance between proinflammation and anti-inflammation cytokines (i) Li and He, [40] Th17 cell, ILCs (i) IL17 signaling is able to induce a cascade of proinflammatory molecules like TNF, IFNγ, IL22, lymphotoxin, IL1β, and lipopolysaccharide (LPS). IL17A is known to mediate signaling synergistically to drive expression of inflammatory genes (ii) Activated by IL-23 pathway as followed: when IL23 binds to its receptor, Jak2 and Tyk2 kinases are activated.…”