Deoxyspergualin is an immunosuppressive
drug which is effective in both preventing allograft rejection and suppressing
steroid-resistant acute rejection. This study was designed to determine whether
deoxyspergualin could suppress the development of rapidly progressive crescentic
glomerulonephritis in
antigen-primed animals. Accelerated anti-glomerular basement membrane (GBM)
glomerulonephritis was induced by priming rats with rabbit
immunoglobulin G (
IgG), followed 5 days later by an injection of rabbit anti-rat GBM serum (day 0). Groups of five animals were treated with
deoxyspergualin (5 mg/kg.day) or saline by daily ip injection from day 0 until
euthanasia on days 1, 7, 14, or 21.
Deoxyspergualin treatment resulted in a significant suppression of renal disease. Compared with saline-treated controls,
deoxyspergualin treatment reduced
proteinuria, resolved
hematuria, and completely prevented a fall in
creatinine clearance. Deposition of rabbit
IgG along the GBM was unaffected by
deoxyspergualin treatment, but glomerular deposition of rat
IgG and C3 was significantly reduced from day 14 onwards, which was associated with a significant reduction of circulating rat anti-rabbit
IgG.
Deoxyspergualin treatment also produced a dramatic improvement in renal histology.
Glomerular necrosis,
fibrosis, and crescent formation were markedly suppressed, whereas tubulointerstitial lesions were completely prevented. This was associated with a marked suppression of mononuclear cell infiltration and activation. In the glomerulus, macrophage infiltration was suppressed by approximately 50%, whereas accumulation of macrophages and immune-activated (interleukin-2 receptor) T cells within the interstitium was almost completely abrogated by
deoxyspergualin treatment. In conclusion,
deoxyspergualin was found to be effective in suppressing the development of experimental crescentic
glomerulonephritis in
antigen-primed animals by acting on both the local cell-mediated response within the kidney and the systemic humoral immune response. Further work is warranted to determine whether this could be a useful
drug for the treatment of human proliferative
glomerulonephritis.