Leukocyte traffic control: a novel therapeutic strategy for inflammatory bowel disease.
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.
Fiorino
Gionata
G
IBD Unit, Division of Gastroenterology and Digestive Endoscopy, IRCCS Humanitas, Rozzano, Milan, Italy.
Correale
Carmen
C
Fries
Walter
W
Repici
Alessandro
A
Malesci
Alberto
A
Danese
Silvio
S
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002986:Clinical Trials as Topic; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D039441:Integrin alpha4 / Q000276:immunology; D036904:Leukocyte Rolling / Q000187:drug effects*; D000069442:Natalizumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab; D039441:Integrin alpha4; C543529:vedolizumab