The mechanism of action of corticosteroids on glomerular injury in acute serum sickness in rabbits.
Macrophages have recently been identified as the predominant mediators of the glomerular injury in acute serum sickness (AcSS) in rabbits. Corticosteroids have been shown to prevent this lesion, but the mechanism of this effect is unknown. As corticosteroids are potent anti-macrophage agents, the effect of prednisolone treatment (2 mg/kg/day) on glomerular macrophage accumulation and injury was assessed in rabbits developing AcSS. Eleven untreated animals all developed a proliferative endocapillary glomerulonephritis (mean 71.7 +/- 1.9 sem cells per glomerular cross section, c/gcs) with glomerular macrophage accumulation (46.3 +/- 5.7 macrophages per glomerulus, macs/glom) and proteinuria (555 +/- 379 mg/24 h). Eight animals were treated with prednisolone commencing not more than 48 h prior to immune elimination (IE). Glomerular injury was markedly attenuated with significantly less cellular proliferation (49.1 +/- 2.1 c/gcs, P less than .005), fewer macrophages within glomeruli (10.5 +/- 7.7 macs/glom, P less than .005) and minimal proteinuria (19.3 +/- 5.5 mg/24 h, P less than 0.01). Treatment did not alter the amount of circulating BSA-anti-BSA immune complex; its time of IE (11.1 +/- 0.4 days treated, 11.4 +/- 0.4 days untreated) its renal deposition (2.36 +/- 0.64 micrograms BSA/g renal cortex treated, 2.66 +/- 0.52 mg BSA/g renal cortex untreated) or its glomerular localization. These results indicate that prednisolone treatment can effectively reduce the glomerular injury of AcSS. This effect is not dependent on any alteration of immune complex formation or deposition, but involves reduction of macrophage accumulation at the inflammatory site.
D000208:Acute Disease; D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D007668:Kidney / Q000276:immunology; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D009000:Monocytes / Q000187:drug effects; D011239:Prednisolone / Q000627:therapeutic use*; D011817:Rabbits; D012713:Serum Sickness / Q000150:complications*
D000936:Antigen-Antibody Complex; D011239:Prednisolone