Abstract
The effects of cyclophosphamide an antinuclear antibody levels, immune complex deposition in renal glomeruli, glomerular cell proliferation and glomerulosclerosis in the (NZB x NZW)F1 hybrid mouse have been investigated in order to better understand the mechanism of action of this drug on nephritis. Five groups of mice were injected daily with this agent (15 mg/kg) by the i.p. route over a 2-month period. Treatment periods began at 1, 3, 5, 7 and 9 months. Each group was killed at the end of the treatment period. During the last week [3H]Tdr(1 mu Ci/g) was injected daily i.p. Immune complex deposition was measured by quantification of glomerular immunofluorescent staining in both capillary loops and mesangium. Glomerular cell proliferation was quantified by measurement of the number of glomerular cells which incorporated [3H]Tdr during in vivo labelling. The number of [3H]Tdr-labelled cells in each of 100 glomeruli was counted using kidney autoradiographs of whole kidney slices. This technique provided a very reproducible and quantitative index of glomerular cell proliferation. Glomerulosclerosis was measured by determining percentage of PAS-positive material in each of 100 counted glomeruli. Immune complex deposition in the kidney preceded the glomerular cell proliferation. The proliferation reached a peak at 9 months of age. Glomerulosclerosis gradually increased with age until the animal's death. Cyclophosphamide significantly decreased antinuclear antibody levels, glomerular cell proliferation, and immunoglobulin staining in the glomeruli. Progression of glomerulosclerosis was significantly arrested. The present findings demonstrate a very significant effect of cyclophosphamide on three important pathological changes which occur in the nephritis of the (NZB x NZW)F1 hybrid mouse and provide information about possible mechanisms underlying these changes.
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