Glomerular tumor necrosis factor and interleukin 1 during acute aminonucleoside nephrosis. An immunohistochemical study.

Acute aminonucleoside nephrosis progresses to glomerulosclerosis. The mechanisms for this phenomenon are not entirely known. Our objectives were to identify macrophage (m phi)-derived peptide growth factors (i.e., tumor necrosis factor and interleukin 1), using immunohistochemical means, in glomeruli of rats with acute aminonucleoside nephrosis. Recently, a role for glomerular m phi s has been suggested as one of the possible mechanisms responsible for this transition from acute glomerular injury to glomerulosclerosis. Since peptide growth factors are elaborated by m phi s and produce alterations in mesangial cell proliferation and protein biosynthesis, we investigated whether these cytokines were present in glomeruli during aminonucleoside nephrosis, which has been typically regarded as a nonimmune toxic glomerulopathy. Fourteen days after puromycin aminonucleoside (PA) delivery, nephrotic control rats (PA/control) and nephrotic animals that had been maintained on an essential fatty acid-deficient (EFAD) diet (PA/EFAD) for 8 weeks before PA, manifested cytoplasmic tumor necrosis factor and interleukin 1 within cells located in the glomerular mesangium as detected by immunohistochemical means. Despite equivalent levels of albuminuria and fasting total cholesterol during peak nephrosis, the PA/EFAD rats had significant reductions in the number of tumor necrosis factor-positive glomerular cells (1.8 +/- 0.1 versus 8.5 +/- 0.4, p less than .001) and interleukin 1-positive glomerular cells (1.5 +/- 0.1 versus 7.2 +/- 0.5, p less than .001) in comparison with the PA/control group. These data correlated with a reduction in the number of ED-1-positive cells (i.e. glomerular m phi s) in glomeruli of PA/EFAD animals as compared with PA/control rats (2.2 +/- 0.3 versus 10.9 +/- 1.4, p less than .001), suggesting that m phi-derived peptide growth factors may be important determinants in initiating a pathobiologic sequence culminating in glomerulosclerosis in this model.