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Lab Invest. 1991 Jan;64(1):21-8.

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

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1
Division of Nephrology, Milton S. Hershey Medical Center, Hershey, Pennsylvania.

Abstract

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.

PMID:
1990206
[Indexed for MEDLINE]

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