Leukocyte Traffic Control

A Novel Therapeutic Strategy for Inflammatory Bowel Disease

An Update

Monica Cesarini; Gionata Fiorino

Disclosures

Expert Rev Clin Immunol. 2013;9(4):301-306. 

In This Article

Abstract and Introduction

Abstract

Adhesion molecules play a key role in the pathogenetic mechanisms of inflammatory bowel disease (IBD), both in Crohn's disease (CD) and ulcerative colitis (UC). In the last decade, some progress has been made in understanding their key role in leukocyte trafficking control in terms of basic research, but evidence of clinical efficacy is lacking. In the last 2 years, new molecules directed against integrins and integrin receptors have been developed and investigated in clinical trials, showing that anti-α4β7 integrin agents can be effective and safe for the induction and maintenance of remission in active CD and UC. Preliminary data show that anti-MAdCAM, anti-β7 and anti-integrin receptor agents are not all effective in IBD. Such results open new perspectives on clinical management of IBD, and new directions in understanding the role of adhesion molecules and leukocyte recruitment both in CD and UC.

Introduction

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) with unknown etiology and not well established pathogenetic mechanisms. Several mechanisms seem to be involved in the pathogenesis of these diseases: a combination of genetic basis and environmental factors, dysregulation of the intestinal barrier function and the intestinal homeostasis by infiltrating leukocytes in the mucosa, and neoangiogenesis are thought to play a fundamental role.[1–3]

Integrins are a family of heterodimeric transmembrane receptors that are constitutively expressed. At least 24 different integrins have been identified on the surface of leukocytes whose different combination of a and b subunits results in a variety of adherence specificity.[4] However, only five modulate leukocyte–endothelial cell adhesion: the β1, β2 and β7 subfamilies (α1β2, α2β1, α3β1, α4β1 and α4β7).

Although advances in basic science regarding the new potential therapeutic targets have been done, the anti-TNF-α agents are the only biological agents currently available in Europe for IBD, which may indirectly block mechanisms of leukocyte recruitment, through inhibiting angiogenesis.[5]

Recent advances in the development of new molecules, able to interfere with leukocyte recruitment into the gut, show that the pharmacological inhibition of integrins or chemokine receptors may result in clinical efficacy both in active CD and UC.

Comments

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