GLYCEROL INDUCED ARF IN RATS IS MEDIATED BY TUMOR-NECROSIS-FACTOR-ALPHA

Glycerol-induced acute renal failure (ARF) in rats is a model of acute trauma in which intra-muscular injection of 50% glycerol causes rapid myoglobinuria, oliguria, and a rapid reduction in glomerular filtrati on rate. We found that plasma tumor necrosis factor-alpha (TNF-alpha) is rapidly induced in glycerol injected rats. It can be detected in so me animals as early as 30 minutes post-injection, peaks at one hour (r ange: 4 to 32 U/ml) with no significant difference between blood from renal vein and vena cava, and decreases by three hours. None was detec ted in control saline injected rats (P < 0.001). Four out of five rats infused with neutralizing anti-TNF-alpha antiserum (200 mul/300 g bod y wt) immediately prior to glycerol injection had significantly protec ted kidney function (P = 0.001). In these rats, plasma urea (104.8 +/- 58.9 mg%) and creatinine (1.16 +/- 0.38 mg%) were lower and creatinin e clearance higher (0.34 +/- 011 ml/min) than in glycerol injected ani mals pretreated with normal serum (291.8 +/- 41.8 mg%, 3.15 +/- 0.74 m g%, and 0.03 +/- 0.03 ml/min, respectively) or animals injected with g lycerol alone (302.6 +/- 76.8 mg%, 3.45 +/- 0.97 mg%, and 0.03 +/- 0.0 3 ml/min, respectively). These results imply a direct role for TNF-alp ha in pathogenesis of glycerol induced ARF in rats.