ALTERED GLOMERULAR STEADY-STATE LEVELS OF TUMOR-NECROSIS-FACTOR-ALPHA MESSENGER-RNA DURING NEPHROTIC AND SCLEROTIC PHASES OF PUROMYCIN AMINONUCLEOSIDE NEPHROSIS IN RATS

1. We determined glomerular and medullary tumour necrosis factor-alpha mRNA levels in acute puromycin aminonucleoside nephrosis on days 0, 8 and 20. 2. Tumour necrosis factor-alpha mRNA levels were increased fourfold in glomeruli and twofold in the medulla during the nephrotic stage of acute puromycin aminonucleoside nephrosis (day 8). 3. The high tumour necrosis factor-alpha mRNA levels in both glomeruli and the medulla were ameliorated significantly by methylprednisolone administration. 4. Focal glomerular sclerosis was induced in rats by injection of puromycin aminonucleoside on days 0, 27, 34 and 41 and by unilateral nephrectomy on day 22. 5. The percentage of sclerosing glomeruli was 16.6% on day 48 and had increased significantly to 72.8% on day 80. 6. During the sclerotic phase of puromycin aminonucleoside nephrosis, glomerular tumour necrosis factor-alpha mRNA levels increased as glomerular sclerosis progressed. On day 80, glomerular tumour necrosis factor-alpha mRNA levels were 13-fold higher than levels in control rats. 7. These data suggest that glomerular tumour necrosis factor-alpha mRNA expression is associated with the development of puromycin aminonucleoside-induced glomerular sclerosis.