Bench to bedside: Tumor necrosis factor-alpha: From inflammation to resuscitation

Proinflammatory mediators such as tumor necrosis factor-alpha (TNF) have be en implicated in the pathophysiology in a number of acute disease states. T umor necrosis factor-alpha can contribute to cell death, apoptosis, and org an dysfunction. Tumor necrosis factor-alpha can be generated with sepsis or ischemia-reperfusion by activation of cell mitogen-activated protein kinas es and nuclear factor kappa B, leading to TNF production. A number of strat egies to modulate TNF have been recently explored, including factors direct ed toward mitogen-activated protein kinases, TNF transcription, anti-inflam matory ligands, heat shock proteins, and TNF-binding proteins. However, TNF may also play an important role in the adaptive response to injury and inf lammation. Control of the deleterious effects of TNF and other proinflamato ry cytokines represents a realistic goal for clinical emergency medicine. T he purpose of this article is to provide a background of relevance to emerg ency medicine academicians on the production and regulation of TNF, the acu te effects of TNF on pathophysiology, and the rationale for therapeutic int erventions directed toward TNF and the clinical experience with these strat egies.