Leukocyte traffic control: a novel therapeutic strategy for inflammatory bowel disease

Abstract

Inflammatory bowel diseases share common pathogenetic mechanisms that are not yet completely understood. It is clear, however, that the expression and production of cytokines in response to inflammation plays a key role in mediating the migration of activated leukocytes. The process of angiogenesis and the expression of adhesion molecules on the intestinal microvasculature act as gateways, facilitating the recruitment of leukocytes into the gut mucosa. New agents specifically blocking adhesion molecules, in particular integrins, have been developed in order to limit the passage of activated leukocytes into the mucosa. Non-gut-specific anti-integrin agents, such as natalizumab, have been shown to be effective in the treatment of IBD, but the risk of serious adverse events has limited their further development. The development of a new specific molecule, vedolizumab, is currently under investigation in a large clinical trial. This novel specific anti-integrin drug seems to hold promise in the treatment of gut inflammation.

Keywords::

• α4β7
• adhesion
• angiogenesis
• CAM
• Crohn’s disease
• inflammatory bowel disease
• integrin
• MAdCAM
• molecules
• natalizumab
• ulcerative colitis
• vedolizumab

Financial & competing interests disclosure

Silvio Danese has served as a consultant for Takeda Millennium. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.