Study of tumor necrosis factor receptor in the inflammatory bowel disease

Abstract

Ulcerative colitis (UC) and Crohn’s disease (CD) are part of Inflammatory Bowel Diseases (IBD) and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells. In addition, the main inflammatory mediator is related to the tumor necrosis factor-alpha (TNF-α). TNF-α is a me-diator of the intestinal inflammatory processes, thus being one of the main cytokines involved in the pathogenesis of IBD, however, its levels, when measured, are present in the serum of patients with IBD. In addition, TNF-α plays an important role in promoting inflammation, such as the production of interleukins (IL), for instance IL-1β and IL-6. There are two receptors for TNF as following: The tumor necrosis factor 1 receptor (TNFR1); and the tumor necrosis factor 2 receptor (TNFR2). They are involved in the pathogenesis of IBD and their receptors have been detected in IBD and their expression is correlated with disease activity. The soluble TNF form binds to the TNFR1 receptor with, and its activation results in a signaling cascade effects such as apoptosis, cell proliferation and cytokine secretion. In contrast, the transmembrane TNF form can bind both to TNFR1 and TNFR2. Recent studies have suggested that TNF-α is one of the main pro-inflammatory cytokines involved in the pathogenesis of IBD, since TNF levels are present in the serum of both patients with UC and CD. Intravenous and subcutaneous biologics targeting TNF-α have revolutionized the treatment of IBD, thus becoming the best available agents to induce and maintain IBD remission. The application of antibodies aimed at neutralizing TNF-α in patients with IBD that induce a satisfactory clinical response in up to 60% of patients, and also induced long-term maintenance of disease remission in most patients. It has been suggested that anti-TNF-α agents inactivate the pro-inflammatory cytokine TNF-α by direct neutralization, i.e., resulting in suppression of inflammation. However, anti-TNF-α antibodies perform more complex functions than a simple blockade.

Keywords: Tumor necrosis factor 1 receptor; Tumor necrosis factor 2 receptor; Inflammatory bowel diseases; Enteric nervous system; tumor necrosis factor-alpha

Core Tip: This review summarizes the role of Tumor Necrosis Factor-alpha (TNF-α) in promoting inflammation. Studies have suggested that TNF-α is one of the main pro-inflammatory cytokines involved in the pathogenesis of Inflammatory Bowel Diseases (IBD). In addition, the enteric nervous system is affected by IBD. There are two receptors for TNF: The tumor necrosis factor 1 receptor; and the tumor necrosis factor 2 receptor. They are involved in the pathogenesis of IBD. The application of antibodies aimed at neutralizing TNF-α in patients with IBD induce a satisfactory clinical recovery. This review addresses the main aspects of TNF-α in IBD and anti-TNF therapies.