Tumor necrosis factor-alpha antagonism improves vasodilation during hyperinsulinemia in metabolic syndrome.

Abstract

OBJECTIVE:

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

RESEARCH DESIGN AND METHODS:

Vascular responses to intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in patients with metabolic syndrome, before and after administration of infliximab.

RESULTS:

Patients had blunted vasodilator responses to ACh and SNP during hyperinsulinemia compared with control subjects; 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 metabolic syndrome, but its effect was not further enhanced by concurrent administration of infliximab.

CONCLUSIONS:

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

• Authors: Manfredi Tesauro, Francesca Schinzari, Valentina Rovella, Domenico Melina, Nadia Mores, Angela Barini, Marco Mettimano, Davide Lauro, Micaela Iantorno, Michael J Quon, Carmine Cardillo
• Journal: Diabetes care (Diabetes Care) Vol. 31 Issue 7 Pg. 1439-41 (Jul 2008) ISSN: 1935-5548 [Electronic] United States
• PMID: 18390795 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Antibodies, Monoclonal
• Blood Glucose
• Triglycerides
• Tumor Necrosis Factor-alpha
• Nitroprusside
• Cholesterol
• Infliximab
• Acetylcholine

Topics

• Acetylcholine (pharmacology)
• Analysis of Variance
• Anti-Inflammatory Agents (therapeutic use)
• Antibodies, Monoclonal (therapeutic use)
• Blood Glucose (metabolism)
• Cholesterol (blood)
• Humans
• Hyperinsulinism (drug therapy, physiopathology)
• Infliximab
• Metabolic Syndrome (drug therapy, physiopathology)
• Nitroprusside (pharmacology)
• Reference Values
• Triglycerides (blood)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)
• Vasodilation (drug effects)