Tumor Necrosis Factor‐α Antagonism Improves Endothelial Dysfunction in Patients With Crohn's Disease

This study assessed the presence of endothelial dysfunction in patients with inflammatory bowel diseases (IBDs) and evaluated the possible role of tumor necrosis factor (TNF)-a in the pathophysiology of this abnormality. Similar elevations in circulating markers of inflammation (C-reactive protein and interleukin-6) were observed in Crohn’s disease and ulcerative colitis compared to controls. Endothelium-dependent vasodilation to acetylcholine was impaired in Crohn’s disease, but not in ulcerative colitis. Endothelium-independent vasodilation to sodium nitroprusside, by contrast, was not different among the three groups. The TNF-a neutralizing antibody, infliximab, enhanced the responsiveness to acetylcholine, but not to nitroprusside, in Crohn’s disease, without modifying vascular responses to both drugs in ulcerative colitis. In conclusion, despite comparable degrees of systemic inflammation in the two IBDs, endothelial dysfunction is a selective feature of Crohn’s disease and is beneficially affected by intravascular TNF-a neutralization. These findings underscore the role of selective cytokine targeting in improving endothelial function in patients with Crohn’s disease. Idiopathic inflammatory bowel diseases (IBDs) are associated with local activation of immune cells and dysregulation of several cytokines, which leads to a state of chronic inflammation that may spread systemically from the intestinal wall even during the ‘‘quiescent’’ phases of the disease. Although Crohn’s disease and ulcerative colitis seem to be characterized by different patterns of lymphocyte activation and immunologic responses, 1 overexpression of inflammatory cytokines like tumor necrosis factor (TNF)-a appears to be a common effector mechanism of intestinal damage in both IBDs. 2 This notion has led to the development of novel therapeutic strategies to specifically block this cytokine that have proven effective in both Crohn’s disease 3,4 and ulcerative colitis. 5