ROLE OF NEUTROPHILS AND MACROPHAGES IN EXPERIMENTAL NEPHROSIS OF THE RAT

The single dose administration of the aminonucleoside of puromycin (PA N) induces a nephrotic syndrome in rats characterized by massive prote inuria and progressive histologic changes. This model of acute parench ymal nephritis is thought to be mediated by the renal recruitment of m onocytes and macrophages. To investigate the role of leukocytes in the experimental nephrotic syndrome model, the effects of two methylxanth ines, pentoxifylline (45 mg/kg i.p. twice daily) and torbafylline (5 m g/kg i.p. twice daily) were compared with controls over a 2-week perio d. Pentoxifylline treatment was associated with 3- and 6-fold reductio ns in urinary protein excretion at 7 and 14 days, respectively, compar ed with PAN-treated control animals (p < .01). Similarly, 14-day dosin g of torbafylline resulted in a 3-fold decrease in urinary protein exc retion. Glomerular filtration and electrolyte excretion rates were sim ilar between all treatment groups. There were significant reductions i n glomerular neutrophil and macro-phage counts, but not T-cells (OX19) or suppressor/cytotoxic T-cells (OX8+), in kidneys of rats given eit her treatment compared with PAN con-trol rats. In summary, both pentox ifylline and torbafylline attenuated the proteinuria and glomerular ma crophage and neutrophil infiltration associated with PAN administratio n These data support the role of macrophages and neutrophils in the pa thogenesis of acute parenchymal injury and the potential role of pento xifylline or related analogues in the attenuation of the ensuing renal deficit associated with minimal lesion disease.