RAPID RESOLUTION OF CHRONIC COLITIS IN THE COTTON-TOP TAMARIN WITH ANANTIBODY TO A GUT-HOMING INTEGRIN ALPHA-4-BETA-7

Background & Aims: Integrins play diverse roles in cellular actions an d signaling in the immune system, In the context of mucosal immune res ponses, the integrin alpha 4 beta 7 has received particular attention because of its intimate involvement in lymphocyte recruitment to norma l gastrointestinal mucosa and associated lymphoid tissue, The aim of t his study was to determine the functional relevance of alpha 4 beta 7 in the pathogenesis of colonic inflammatory disease using the colitic cotton-top tamarin, an animal model of human ulcerative colitis. Metho ds: Chronically colitic cotton-top tamarins were given either a cross- reactive monoclonal antibody to human alpha 4 beta 7 or an irrelevant control monoclonal antibody. The animals were then evaluated clinicall y and mucosal biopsy specimens assessed by histological and quantitati ve morphometric analysis. Results: A blocking monoclonal antibody to a lpha 4 beta 7 integrin ameliorated inflammatory activity and rapidly i mproved stool consistency when administered to chronically colitic ani mals. Furthermore, using morphometric analysis of biopsy specimens, an tibody therapy reduced the mucosal density of alpha 4 beta 7(+) lympho cytes and alpha 4 beta 7(-) neutrophils and macrophages. Conclusions: These results suggest that the alpha 4 beta 7 integrin represents a no vel, potentially organ-specific therapeutic target for the treatment o f inflammatory bowel disease.