TNF- -dependent bilateral renal injury is induced by unilateral renal ischemia-reperfusion

Meldrum, Kirstan K., Daniel R. Meldrum, Xianzhong Meng, Lihua Ao, and Alden H. Harken. TNF-dependent bilateral renal injury is induced by unilateral renal ischemiareperfusion. Am J Physiol Heart Circ Physiol 282: H540–H546, 2002; 10.1152/ajpheart.00072.2001.—While tumor necrosis factor (TNF)is an important mediator of renal ischemiareperfusion (I/R) injury, its role in contralateral renal injury after isolated renal ischemia remains unknown. We therefore investigated the effect of isolated left renal ischemia on the nonischemic contralateral kidney. To study this, male Sprague-Dawley rats were anesthetized and exposed to varying degrees of left renal I/R injury. Both kidneys were subsequently harvested, serum samples were obtained, and TNFprotein expression (ELISA), TNFmRNA content (RT-PCR), TNFimmunolocalization, and neutrophil infiltration (myeloperoxidase assay) were determined. The effect of TNFon neutrophil infiltration was assessed by neutralizing TNFwith TNF binding protein (TNF-BP) before left renal I/R injury. TNFprotein expression, TNFmRNA induction, and neutrophil infiltration increased significantly in both kidneys after unilateral renal I/R injury. Furthermore, the administration of TNF-BP before unilateral renal I/R substantially reduced the degree of neutrophil infiltration bilaterally. These results constitute the initial demonstration that unilateral renal I/R induces bilateral TNFproduction and neutrophil infiltration through a TNF-dependent mechanism.