Differential effects of steroids on leukocyte-mediated glomerulonephritis in the rabbit
Abstract:
The effects of steroids on the development of injury in two models of experimental glomerulonephritis (GN), (one mediated by neutrophils, the other by macrophages) were compared. The neutrophil-associated lesion [initiated by heterologous antiglomerular basement membrane (GBM) antibody] was characterized by the development of an exudative endocapillary GN with heavy neutrophil accumulation [mean, 6.9 neutrophils/glomerular cross section (N/GCS) +/- 2.9 SD], minor macrophage infiltration [7.9 macrophages/glomerulus (M/G) +/- 2.2 SD] and heavy proteinuria (1905 mg/24 hr +/- 520 SD). Steroid-treated (methylprednisolone, 2 mg/kg/12 hr i.v.) rabbits developed a marked monocytopenia, mild neutrophilia, and significant reduction in glomerular macrophage accumulation (0.3 M/G 0.02 SD). However, neutrophil accumulation (6.1 N/CGS +/- 2.5 SD), histological appearances, and proteinuria (1820 mg/hr +/- 490 SD) were unaffected. The macrophage-associated model of GN was induced by passive autologous rabbit anti-sheep IgG 15 hr after the injection of a subnephritogenic dose of the same anti-GBM antibody. The glomerular lesion was characterized by a diffuse endocapillary proliferative GN with heavy macrophage infiltration (54 M/G +/- 8 SD), insignificant neutrophil accumulation (0.8 N/GCS 0.02 SD), and the regular development of proteinuria (420 mg/24 hr +/- 80 SD). Steroid-treated rabbits developed a mild neutrophilia and a significant monocytopenia associated with abrogation of glomerular macrophage accumulation (2.3 M/G +/- 0.8 SD). This was associated with the prevention of the development of GN and proteinuria (22 +/- 9.5 SD). Thus, steroids produce monocytopenia and prevent glomerular macrophage accumulation and associated injury whereas neutrophil accumulation and injury is unaffected. These data suggest steroids may have widely varying effects on the outcome of leukocyte-associated experimental GN depending on the nature of the infiltrating cells.
