THE EXPRESSION OF MESSENGER-RNA FOR TUMOR-NECROSIS-FACTOR-ALPHA INCREASES IN THE OBSTRUCTED KIDNEY OF RATS SOON AFTER UNILATERAL URETERAL LIGATION

Cytokines, including transforming growth factor (TGF)-beta 1, contribu te to the tubulointerstitial fibrosis of ureteral obstruction. Tumour necrosis factor (TNF)-alpha, a proinflammatory cytokine produced by mu ltiple cells including macrophages and resident renal cells, has a rol e in inflammatory cell recruitment in glomerular injury. We measured T NF-alpha mRNA in the renal cortex of rats at different times after the onset of unilateral ureteral obstruction (UUO) and determined whether angiotensin II (AngII) inhibition or total body irradiation affects t he mRNA levels of TNF-alpha. Rats were killed at 1, 2, 4, 24, 72 and 1 20 h after UUO. Levels of TNF-alpha mRNA increased significantly in th e obstructed kidney at 1 h (x 2), 2 h (x 2.7), 4 h (x 3.6), 24 h (x 2. 7), 72 h (x 1.8) and 120 h (x 2.8) after ureteral ligation when compar ed to the contralateral kidney of the same animals or to control (norm al) kidneys. Tumour necrosis factor-alpha mRNA increased in renal cort ical tubules but not in glomeruli. Treatment with enalapril, an angiot ensin-converting enzyme (ACE) inhibitor, before and after UUO decrease d TNF-alpha mRNA levels in the obstructed kidney by about: 40% at 4 h after the onset of UUO, but at 120 h there was no difference in TNF-al pha levels in the obstructed kidney of treated and untreated animals. Total body irradiation, which depletes macrophages in the obstructed k idney, did not prevent the upregulation of TNF-alpha mRNA expression a t 4 h after UUO. Thus, TNF-alpha may have a role in initiating tubuloi nterstitial injury in the obstructed kidney. Leucocytes infiltrating t he renal interstitium of the obstructed kidney do not appear to contri bute to the increased mRNA expression of TNF-alpha. Angiotensin II may contribute, at least in part, to the early increased expression of TN F-alpha mRNA in the obstructed kidney.