Treatment of murine lupus nephritis with cyclophosphamide or total lymphoid irradiation

Untreated 9 to 11 month-old, female NZB/W F1 mice all died within six weeks (wks) after the occurrence of nephrotic range proteinuria (greater than or equal to 3 g/liter). Significant prolonged survival could be obtained in similar groups of animals either by weekly i.v. pulses of cyclophosphamide (CY, 25 mg/kg, 40% survival 20 wks after start of treatment) or by administering total lymphoid irradiation (TLI, 17 daily fractions of 2 Gy, 70% survival at 20 wks). All surviving animals in both groups showed remission of the nephrotic range proteinuria. In all treated mice, light microscopy examination of the kidneys revealed a decrease of inflammation and a stabilization of proliferation and sclerosis, yet immunofluorescence for IgM, IgG and C3 was not significantly altered. The better survival of the TLI- as compared to the CY-treated mice (P less than 0.001) was due to a lower incidence of lymphomas or viral infections. IgG anti-DNA auto-antibodies were significantly lowered by CY but not by TLI treatment. It is concluded that CY pulse therapy and TLI are both efficient treatment modalities for high grade lupus like NZB/W disease. In this model TLI is safer than CY when used in a dose regimen of 25 mg/kg/wk and interferes with the course of the disease without lowering the IgG anti-DNA antibodies.