The role of tumor necrosis factor in renal ischemia-reperfusion injury

Renal ischemia-reperfusion injury induces a cascade of events leading to ce llular damage and organ dysfunction. Tumor necrosis factor-alpha (TNF), a p otent proinflammatory cytokine, is released from the kidney in response to, and has been implicated in the pathogenesis of, renal ischemia-reperfusion injury. TNF induces glomerular fibrin. deposition, cellular infiltration a nd vasoconstriction, leading to a reduction in glomerular filtration rate ( GFR). The signaling cascade through which renal ischemia-reperfusion induce s TNF production is beginning to be elucidated. Oxidants released following reperfusion activate p38 mitogen activated protein kinase (p38 MAP kinase) and the TNF transcription factor, NF kappa B, leading to subsequent TNF sy nthesis. In a positive feedback, proinflammatory fashion, binding of TNF to specific TNF membrane receptors can reactivate NF kappa B. This provides a mechanism by which TNF can upregulate its own expression as well as facili tate the expression of other genes pivotal to the inflammatory response. TN F receptor binding can also induce renal cell apoptosis, the major form of cell death associated with renal ischemia-reperfusion injury. Anti-TNF stra tegies targeting p38 MAP kinase, NF kappa B, and TNF itself are being inves tigated as methods of attenuating renal ischemic injury. The control of TNF production and activity represents a realistic goal for clinical medicine.