Differential effects of 6-mercaptopurine and cyclophosphamide on autoimmune phenomena in NZB mice

Abstract

The effects of 6-mercaptopurine (7·5 mg/kg) and cyclophosphamide (15 mg/kg and 30 mg/kg) on various aspects of the immune response have been compared in New Zealand Black (NZB) mice. Injections were given daily for 5–8 weeks. Serologic and morphologic studies during and after treatment revealed the following: (1) 6-MP decreased the levels of circulating polymorphonuclear leucocytes, monocytes, and large lymphocytes; small and medium lymphocyte counts remained unchanged. In contrast, cyclophosphamide decreased mainly the small and medium lymphocytes, leaving the other cell types unchanged. (2) In older animals, 6-MP produced a marked fall in haematocrit, while cyclophosphamide did not do so. (3) Cyclophosphamide delayed the onset of Coombs positivity and decreased the Coombs antibody titre. It also decreased immunofluorescent staining of γ-globulin deposits in the kidney. 6-MP had no such effects.

The results suggest that 6-MP exerted an anti-proliferative action on the bone marrow, as shown by a decrease of short-lived cells in the blood. Cyclophosphamide, on the other hand, appeared to have mainly a cytotoxic effect on circulating cells, resulting in depletion of the long-lived small lymphocytes of the blood and leading to inhibition of autoantibody formation and immune complex deposition in the kidney. Cyclophosphamide would, therefore, appear to be the preferable drug where suppression of ongoing cellular and humoral immune reactions is desirable.