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TNF- Antagonism Improves Vasodilation During Hyperinsulinemia in Metabolic Syndrome

Manfredi Tesauro, MD^*, Francesca Schinzari, MD, Valentina Rovella, MD^*, Domenico Melina, MD, Nadia Mores, MD, Angela Barini, MD, Marco Mettimano, MD, Davide Lauro, MD, Micaela Iantorno, MD, Michael J. Quon, MD, PhD and Carmine Cardillo, MD

*Università di Tor Vergata, Rome, Italy
Università Cattolica del Sacro Cuore, Rome, Italy; and
NCCAM, NIH, Bethesda, MD, USA

carmine.cardillo{at}rm.unicatt.it

ABSTRACT

Objective: Obesity is associated with chronic inflammation due to overproduction of proinflammatory cytokines, including TNF-. We assessed the effects of TNF- neutralization by infliximab on vascular reactivity during hyperinsulinemia in obesity-related metabolic syndrome (MetS).

Research Design and Methods: Vascular responses to intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in patients with MetS, before and after administration of infliximab.

Results: Patients had blunted vasodilator responses to ACh and SNP during hyperinsulinemia compared with controls; a potentiation of the responsiveness to both ACh and SNP, however, was observed in patients following infliximab. The antioxidant vitamin C improved the vasodilator response to ACh in patients with MetS, but its effect was not further enhanced by concurrent administration of infliximab.

Conclusions: TNF- neutralization ameliorates vascular reactivity in MetS during hyperinsulinemia, likely in relation to decreased oxidative stress, thereby suggesting an involvement of inflammatory cytokines in vascular dysfunction of these patients.

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