title: Glomerular tumor necrosis factor and interleukin 1 during acute aminonucleoside nephrosis. An immunohistochemical study.
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.
authors.affiliation: Division of Nephrology, Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: J R
authors.initials: JR
authors.lastname: Diamond
authors.forename: I
authors.initials: I
authors.lastname: Pesek
mesh_terms: D000818:Animals; D005228:Fatty Acids, Essential / Q000172:deficiency; D005920:Glomerular Mesangium / Q000378:metabolism; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D009401:Nephrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011692:Puromycin Aminonucleoside / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D005228:Fatty Acids, Essential; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D011692:Puromycin Aminonucleoside