Kinetics of tumor necrosis factor α in plasma and the cardioprotective effect of a monoclonal antibody to tumor necrosis factor α in acute myocardial infarction,

Background Inflammation plays a critical role in acute myocardial infarction (AMI) and tumor necrosis factor alpha (TNF-α) is a potent inflammatory trigger. This study was designed to examine the kinetics of TNF-α in plasma in patients with AMI and the potential benefit of inhibition of TNF-α monoclonal antibody in AMI. Methods And Results TNF-α levels in plasma were measured in 42 patients with AMI. TNF-α levels were elevated at 4 hours after onset of chest pain and declined to control values at 48 hours. TNF-α levels were higher in patients with Killip III and IV than in those with Killip I and II (P < .01). To examine the pathogenic role of TNF-α, New Zealand White rabbits were treated with buffer or a TNF-α monoclonal antibody before left anterior descending artery (LAD) ligation. Treatment with the TNF-α monoclonal antibody decreased area of necrosis, number of circulating endothelial cells, and lipid peroxidation product malonaldehyde bis(dimethyl acetal). There was a significant correlation of TNF-α levels with peak CK-MB in AMI patients, and area of necrosis, MDA, and circulating endothelial cells in rabbits (all P < .05). Conclusions TNF-α release early in the course of AMI contributes to myocardial injury and dysfunction. Treatment with the monoclonal antibody against TNF-α can be cardioprotective, particularly in the setting of heart failure in patients with AMI. (Am Heart J 1999;137:1145-52).