Fourteen-week-old female New Zealand B/W F1 mice were treated subcutaneously with 15-deoxyspergualin (DSP) at 0.3 mg-6.0 mg/kg body weight, 4 times/week. They were sacrificed at 36 weeks of age to determine the minimal effective dose as well as the lowest maximally effective dose without toxicity of DSP required to suppress the development of nephropathy. The life span of the animals was significantly prolonged with 0.6 mg/kg or more DSP. Additionally, glomerular (immuno)histological improvement of the kidney at 36 weeks was observed with 0.6 mg/kg DSP, although a higher dose was required to lower serum anti-DNA activity or to decrease proteinuria. In addition, DSP produced a decrease of L3T4+ splenocytes without affecting the number of Lyt 2+ cells, while the level of IL-2 generated in vitro was somewhat elevated. It may be concluded that DSP has a therapeutic range within an order of ten, but its exact mechanism of immunosuppression remains to be determined.
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