Review: Local Tumor Necrosis Factor-α Inhibition in Inflammatory Bowel Disease

Abstract

Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by intestinal inflammation. Increased intestinal levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) are associated with disease activity and severity. Anti-TNF-α therapy is administered systemically and efficacious in the treatment of IBD. However, systemic exposure is associated with adverse events that may impede therapeutic treatment. Clinical studies show that the efficacy correlates with immunological effects localized in the gastrointestinal tract (GIT) as opposed to systemic effects. These data suggest that site-specific TNF-α inhibition in IBD may be efficacious with fewer expected side effects related to systemic exposure. We therefore reviewed the available literature that investigated the efficacy or feasibility of local TNF-α inhibition in IBD. A literature search was performed on PubMed with given search terms and strategy. Of 8739 hits, 48 citations were included in this review. These studies ranged from animal studies to randomized placebo-controlled clinical trials. In these studies, local anti-TNF-α therapy was achieved with antibodies, antisense oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA) and genetically modified organisms. This narrative review summarizes and discusses these approaches in view of the clinical relevance of local TNF-α inhibition in IBD.

Intestinal Inflammation is Linked to Hypoacetylation of Histone 3 Lysine 27 and can be Reversed by Valproic Acid Treatment in Inflammatory Bowel Disease Patients

“…Benefits from biologic therapy for inflammatory bowel disease (IBD) come at a cost of side effects and antidrug antibodies. 1 This necessitates novel anti-inflammatory therapies.…”

TNFɑ-induced LDL cholesterol accumulation involve elevated LDLR cell surface levels and SR-B1 downregulation in human arterial endothelial cells

“…TNF is a pleiotropic autocrine and paracrine mediator important in multiple signaling cascades that range from activating immune cells to ght viruses, bacteria, and cancer cells, to promoting entry of monocytes and lymphocytes into atherosclerotic lesions [4,105,106]. The latter process is recognized to be pro-atherogenic.…”

TNFα-Induced LDL Cholesterol Accumulation Involve Elevated LDLR Cell Surface Levels and SR-B1 Downregulation in Human Arterial Endothelial Cells

“…TNFα is a pleiotropic autocrine and paracrine mediator important in multiple signaling cascades that range from activating immune cells to fight viruses, bacteria, and cancer cells, to promoting entry of monocytes and lymphocytes into atherosclerotic lesions [4,95,96]. The latter process is recognized to be pro-atherogenic.…”