The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) plays a central role in mucosal inflammation and is a key mediator in the inflammatory cascade in both Crohn's disease (CD) and ulcerative colitis (UC). Infliximab, a monoclonal antibody against TNF-alpha has been proved highly effective in the clinical management of both forms of IBD. Aim of this paper is to review the mechanisms of action of infliximab in IBD.
"TNF-α-blocking agents like infliximab induce apoptosis of immune cells, repressing inflammation in severe cases of IBD. Consequently, TNF-α blocking therapy increases the risk of infections and probably also of malignancies [24-26]. However, the absolute risk is small and does not negate the benefits of TNF-α inhibitors in severe Crohn’s disease . "
[Show abstract][Hide abstract] ABSTRACT: A 62 year-old patient with therapy-refractory pouchitis after proctocolectomy for ulcerative colitis was admitted with hematochezia and abdominal discomfort. A malignant melanoma (MM) was found after repeated biopsies of the pouch. Complete staging revealed no evidence for distant metastases and the patient underwent abdominoperineal pouch resection. Six weeks later, the patient was readmitted because of severe general deterioration and diffuse metastatic spread to the liver was found. The patient died of hepatorenal syndrome shortly thereafter.
Patients with inflammatory bowel disease are at increased risk of developing cancer, including rarities such as MM. Our experience stresses the importance of repeated biopsies in therapy-refractory pouchitis.
"The technique of TNF blockade by monoclonal antibodies has been developed as an effective therapy for immune diseases including IBD [14, 15]. As the first monoclonal TNF antibody approved for human treatment, infliximab is a purified, recombinant DNA-derived chimeric human-mouse IgG monoclonal antibody and contains murine heavy (H) and light (L) chain variable regions (VH and VL, resp.), ligated to genomic human heavy and light chain constant regions [14, 16]. Infliximab can quickly form stable complexes with the human soluble or the membrane form of TNF and terminate the biological activity and signals of TNF . "
[Show abstract][Hide abstract] ABSTRACT: The pathogenesis and treatment of inflammatory bowel disease (IBD) have been recently advanced, while it is still challenged with high morbidity and poor prognosis. Infliximab, a monoclonal antibody of tumor necrosis factor (TNF), has emerged as an efficient treatment with many clinical benefits such as quick disease activity reduction and IBD patient life quality improvement. However, the biological effects of infliximab on IBD need to be elucidated. This paper reviewed the clinical use and recently advanced biological action of infliximab on IBD. By forming the stable complex with the soluble or the membrane form of TNF in fluid environment or on cell surface of immune cell, fibroblast, endothelium, and epithelium, infliximab quenches TNF activity and performs the important biological actions which lead to amelioration and remission of immune responses. The mechanisms of infliximab treatment for IBD were intensively discussed. The recent advances on two topics including predictors and side effects of infliximab treatment were also reviewed.
"The debate between uses of cyclosporine or IFX for patients with fulminant UC has been complicated by the complexity of monitoring cyclosporine IV compared to the ease of giving IFX [Janerot et al. 2006]. Additional questions remain regarding the need for long term dosing after anti-TNF induction therapy as ACT studies did not evaluate the long term responses and one may speculate that doses may need adjustment on the long term [Danese et al. 2008; Kohn et al. 2007]. "
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