The Importance of Intestinal Eotaxin-1 in Inflammatory Bowel Disease: New Insights and Possible Therapeutic Implications.

ABSTRACT

BACKGROUND: Involvement of eotaxin-1 in inflammatory bowel disease has been previously suggested and increased levels of eotaxin-1 have been described in both ulcerative colitis and in Crohn's disease. The association between serum levels of eotaxin-1 and that within the colonic mucosa has not been well defined, as is the potential therapeutic value of targeting eotaxin-1. AIMS: To characterize serum and intestinal wall eotaxin-1 levels in various inflammatory bowel disease patients and to explore the effect of targeting eotaxin-1 by specific antibodies in dextran sodium sulfate-induced colitis model. METHODS: Eotaxin-1 levels were measured in colonic biopsies and in the sera of 60 ulcerative colitis patients, Crohn's disease patients and healthy controls. We also followed in experimental colitis the effect of targeting eotaxin-1 by a monoclonal antibody. RESULTS: Colon eotaxin-1 levels were significantly increased in active but not in quiescent ulcerative colitis and Crohn's disease patients compared to healthy controls. Levels of eotaxin-1 in the colon were correlated with eosinophilia only in tissues from active Crohn's disease patients. Our results did not show any statistically significant change in serum eotaxin-1 levels among ulcerative colitis, Crohn's disease and healthy controls. Moreover, we demonstrate that in dextran sodium sulfate-induced colitis, targeting of eotaxin-1 with 2 injections of anti eotaxin-1 monoclonal antibody ameliorates disease activity along with decreasing colon weight and improving histologic inflammation. CONCLUSION: Eotaxin-1 is increasingly recognized as a major mediator of intestinal inflammation. Our preliminary human and animal results further emphasize the value of targeting eotaxin-1 in inflammatory bowel disease.