Novel therapeutics in inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) includes Crohn’s disease and ulcerative colitis. These are chronic disorders of the gut that have no known antigenic triggers and no known cures. However, much has been learned regarding the immunoinflammatory response of these disorders and in the past few years approaches to modulate biological mediators of inflammation have proven somewhat effective. Lymphocytes have a critical role in the ongoing inflammation of IBD. Understanding mechanisms of lymphocyte trafficking to the gut via important adhesion molecule receptors, particularly of the β₂ and β₇ integrins and their immunoglobulin-like receptors such as ICAM-1 and MAdCAM, has defined important differences between IBD and the normal gut. Harnessing these molecules has proved challenging. Defining key cytokines, the inflammatory messengers from these lymphocytes and paradigms of cytokine expression which seem different in Crohn’s disease than in ulcerative colitis has been critical to help target therapies for these diseases. To date, the greatest therapeutic advances have been through modulating TNF-α. However, numerous patents have been issued for a variety of chemicals, mAbs and antisense oligonucleotides that can modulate TNF-α through a variety of mechanisms. This holds true for other key cytokines such as IL-12 and NF-κB. Agents have been developed that allow for direct administration of anti-inflammatory cytokines such as IL-10 or IL-11. This review will present background information on critical adhesion molecules and cytokines in IBD and novel agents in use or recently patented to modulate these factors. Finally, we will review some new methods of modulating intestinal microbes as a means of abrogating the intestinal immune response by minimising its triggers.

• adhesion molecules
• Crohn’s disease
• cytokines
• inflammatory bowel disease
• probiotics
• ulcerative colitis