Abstract
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)-alpha 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-alpha 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-alpha neutralization. These findings underscore the role of selective cytokine targeting in improving endothelial function in patients with Crohn's disease.
Publication types
-
Clinical Trial
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acetylcholine / pharmacology
-
Adult
-
Anti-Inflammatory Agents / pharmacology
-
Anti-Inflammatory Agents / therapeutic use*
-
Antibodies, Monoclonal / pharmacology
-
Antibodies, Monoclonal / therapeutic use*
-
Biomarkers / blood
-
C-Reactive Protein / metabolism
-
Colitis, Ulcerative / blood
-
Colitis, Ulcerative / drug therapy*
-
Colitis, Ulcerative / physiopathology
-
Crohn Disease / blood
-
Crohn Disease / drug therapy*
-
Crohn Disease / physiopathology
-
Dose-Response Relationship, Drug
-
Endothelium, Vascular / drug effects*
-
Endothelium, Vascular / metabolism
-
Endothelium, Vascular / physiopathology
-
Female
-
Gastrointestinal Agents / pharmacology
-
Gastrointestinal Agents / therapeutic use*
-
Humans
-
Infliximab
-
Interleukin-6 / blood
-
Male
-
Middle Aged
-
Nitroprusside / pharmacology
-
Treatment Outcome
-
Tumor Necrosis Factor-alpha / antagonists & inhibitors*
-
Tumor Necrosis Factor-alpha / blood
-
Vasodilation / drug effects*
-
Vasodilator Agents / pharmacology
Substances
-
Anti-Inflammatory Agents
-
Antibodies, Monoclonal
-
Biomarkers
-
Gastrointestinal Agents
-
IL6 protein, human
-
Interleukin-6
-
Tumor Necrosis Factor-alpha
-
Vasodilator Agents
-
Nitroprusside
-
C-Reactive Protein
-
Infliximab
-
Acetylcholine