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- Title
Intravascular tumor necrosis factor α blockade reverses endothelial dysfunction in rheumatoid arthritis<sup>*</sup>.
- Authors
Cardillo, Carmine; Schinzari, Francesca; Mores, Nadia; Mettimano, Marco; Melina, Domenico; Zoli, Angelo; Ferraccioli, Gianfranco
- Abstract
Background: Patients with rheumatoid arthritis (RA) have endothelial dysfunction, which may predispose them to the risk of premature atherosclerosis. This study investigated the involvement of tumor necrosis factor (TNF) α in the pathophysiologic characteristics of this abnormality by use of the TNF-α–neutralizing antibody infliximab.Methods: Endothelium-dependent and -independent vasodilator responses to intra-arterial infusion of increasing doses of acetylcholine and sodium nitroprusside, respectively, were assessed by strain-gauge plethysmography in patients (n = 10) with early RA during saline solution infusion and after intra-arterial infusion of infliximab (200 μg/min).Results: Circulating markers of systemic inflammation (C-reactive protein and interleukin 6) were higher in patients than in control subjects (n = 10, both P < .05), whereas plasma levels of TNF-α and soluble TNF receptor types 1 and 2 were similar in both groups (all P > .05). During saline solution infusion, the vasodilator response to acetylcholine was blunted in patients with RA compared with control subjects (14.2 ± 9.2 mL · min−1 · dL−1 versus 23.7 ± 9.2 mL · min−1 · dL−1 at the highest dose, P = .004) whereas vasodilation to sodium nitroprusside was not different between groups (P = .10). In patients with RA infliximab did not modify circulating C-reactive protein levels (P = .29, versus saline solution) but did potentiate the vasodilator response to acetylcholine (21.0 ± 11.1 mL · min−1 · dL−1; P = .004, versus saline solution). The response to sodium nitroprusside, in contrast, was not modified by infliximab (P = .28 versus saline solution).Conclusions: Intravascular administration of anti–TNF-α antibody ameliorates endothelial function in patients with RA but does not concurrently affect systemic inflammatory changes. Our findings suggest that enhanced TNF-α generation within the vessel wall, rather than systemic mechanisms, plays a role in the pathobiologic features of endothelial dysfunction in RA.Clinical Pharmacology & Therapeutics (2006) 80, 275–281; doi: 10.1016/j.clpt.2006.05.011
- Publication
Clinical Pharmacology & Therapeutics, 2006, Vol 80, Issue 3, p275
- ISSN
0009-9236
- Publication type
Academic Journal
- DOI
10.1016/j.clpt.2006.05.011