Kinetics of tumor necrosis factor alpha in plasma and the cardioprotectiveeffect of a monoclonal antibody to tumor necrosis factor alpha in acute myocardial infarction

Background Inflammation plays a critical role in acute myocardial infarctio n (AMI) and tumor necrosis factor alpha (TNF alpha) is a potent inflammator y trigger. This study was designed to examine the kinetics of TNF-alpha in plasma in patients with AMI and the potential benefit of inhibition of TNF- alpha monoclonal antibody in AMI. Methods and Results TNF-alpha levels in plasma were measured in 42 patients with AMI. TNF-alpha levels were elevated at 4 hours after onset of chest p ain and declined to control values at 48 hours. TNF-alpha levels were highe r in patients with Killip III and IV than in those with Killip I and II (P < .01). To examine the pathogenic role of TNF-alpha, New Zealand White rabb its were treated with buffer or a TNF-alpha monoclonal antibody before left anterior descending artery (LAD) ligation. Treatment with the TNF-alpha mo noclonal antibody decreased area of necrosis, number of circulating endothe lial cells, and lipid peroxidation product malonaldehyde bis(dimethyl aceta l). There was a significant correlation of TNF-alpha levels with peak CK-MB in AMI patients, and area of necrosis, MDA, and circulating endothelial ce lls in rabbits (all P < .05). Conclusions TNF-alpha release early in the course of AMI contributes to myo cardial injury and dysfunction. Treatment with the monoclonal antibody agai nst TNF-alpha can be cardioprotective, particularly in the setting of heart failure in patients with AMI.