Viewpoint Dispatches from the Frontlines of Research—edited by John W. Nelson Matters of the Heart: The Case of TNFα-Targeting Drugs

Drugs targeted at tumor necrosis factor–alpha (TNFα) have paved new avenues for treating chronic inflammatory diseases such as rheumatoid arthritis and many others. Anti-TNFα drugs have been also considered as therapeutics to treat heart failure or other cardiovascular events that are caused or accompanied by high circulating levels of TNFα. Surprisingly, however, anti-TNFα ther-apies caused both beneficial and detrimental cardiovascular effects. Here, we suggest that the disappointing cardiovascular outcome of pharmacological interventions with TNFα-targeted drugs could be reconciled with the Janus-like behavior of TNFα, a molecule that conveys both negative and positive stimuli to the heart. Many drugs developed and approved to treat noncardiovas-cular diseases are known to cause cardiovascular effects that range from arrhythmias to blood pressure disorders, ischemia, heart failure (HF), thromboembolism, or combinations thereof. Drug