The Differential Effects of 6-MP and Cyclophosphamide on Immunoglobulin Deposition in the Skin and Kidney of NZB/NZW F1 Mice

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Abstract
The effects of cyclophosphamide (CY) and 6-mercaptopurine (6-MP) on the accumulation of subepidermal Ig and glomerular Ig in the female NZB/NZW F1 (B/W) mouse were compared. Five-month old female mice, given daily i.p. injections of CY or 6-MP, and untreated control mice were killed after 2 months and specimens obtained for direct immunofluorescent staining of skin and kidney. In addition, electron microscopic examination of the kidneys was performed. Subepidermal Ig was present in 30% of the untreated animals, in none of the CY-treated, and in 83% of the 6-MP treated animals. Glomerular Ig was observed in 81% of the untreated animals, 40% of the CY-treated animals, and 85% of the 6-MP treated animals. ANA tests were positive in 83% of the untreated, 29% of the CY-treated, and 94% of the 6-MP treated animals. All differences between the CY- and 6-MP-treated groups were statistically significant. Electron microscopy of the kidneys demonstrated a marked reduction of electron dense deposits in the CY-treated animals but no reduction was seen in the 6-MP treated animals. These findings showed: 1) CY markedly reduced subepidermal Ig, glomerular Ig, and ANA; and 2) 6-MP increased subepidermal Ig whereas glomerular Ig and ANA remained essentially unchanged. These observations indicate that CY not only appears to be more effective than 6-MP in the treatment of B/W immune complex disease but also that 6-MP enhances Ig deposition in the skin.