REVIEW ARTICLE: THE ROLE OF TUMOR NECROSIS FACTOR IN RENAL ISCHEMIA-REPERFUSION INJURY

AbstractRenal ischemia-reperfusion injury induces a cascade of events leading to cellular damage and organ dysfunction. Tumor necrosis factor-alpha (TNF), a potent 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 and vasoconstriction, leading to a reduction in glomerular filtration rate (GFR). The signaling cascade through which renal ischemia-reperfusion induces 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 synthesis. 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 facilitate the expression of other genes piv...