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


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.
Tesauro
Manfredi
M
Università di Tor Vergata, Rome, Italy.
Schinzari
Francesca
F
Rovella
Valentina
V
Melina
Domenico
D
Mores
Nadia
N
Barini
Angela
A
Mettimano
Marco
M
Lauro
Davide
D
Iantorno
Micaela
M
Quon
Michael J
MJ
Cardillo
Carmine
C
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D006801:Humans; D006946:Hyperinsulinism / Q000188:drug therapy / Q000503:physiopathology*; D000069285:Infliximab; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000503:physiopathology*; D009599:Nitroprusside / Q000494:pharmacology; D012016:Reference Values; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014664:Vasodilation / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D001786:Blood Glucose; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D009599:Nitroprusside; D002784:Cholesterol; D000069285:Infliximab; D000109:Acetylcholine