Suppression of pulmonary injury in experimental 'Goodpasture's syndrome' by deoxyspergualin (DSP).

Abstract

DSP is a potent immunosuppressive drug which can prevent allograft rejection and suppress acute rejection episodes. In this study, the ability of DSP to suppress pulmonary injury in experimental Goodpasture's syndrome was investigated. Passive accelerated anti-glomerular basement membrane (GBM) disease was induced in rats by priming with rabbit IgG, followed 5 days later by injection of rabbit anti-GBM serum (day 0). Groups of five animals were treated with DSP (5 mg/kg intraperitoneally per day) or saline (untreated) from day 0 until being killed on days 1, 7, 14 or 21. At day 1, both DSP-treated and untreated animals exhibited similar pulmonary haemorrhage, oedema, and prominent perivascular leucocyte infiltration. Untreated animals subsequently developed severe widespread pulmonary damage including granulomatous lesions and extensive fibrosis, which correlated with infiltration of macrophages and immune-activated (IL-2R+) mononuclear cells (P < 0.01). Tumour necrosis factor-alpha (TNF-alpha), a known mediator of acute lung damage, was produced by pulmonary mononuclear cells throughout the experimental course. In contrast, DSP treatment resolved pulmonary haemorrhage, prevented the appearance of granulomatous lesions, and resulted in a histologically normal lung structure by day 21. This improvement was associated with a marked suppression of macrophage infiltration (P < 0.001 versus untreated), accumulation of immune activated (IL-2R+) mononuclear cells (P < 0.01 versus untreated), and TNF-alpha production (P < 0.05 versus untreated). DSP treatment also suppressed the deposition of rat anti-rabbit IgG immunoglobulin and C3 along the alveolar basement membrane (P < 0.05 versus untreated). In conclusion, DSP suppressed pulmonary injury in accelerated anti-GBM disease by acting on the local cellular immune response and the systemic humoral immune response. Further studies are warranted to determine whether this could be a useful drug for the treatment of Goodpasture's syndrome in humans.