The kinetics of recovery of leukocyte number and lymphocyte function following an injection of a single high dose of cyclophosphamide in C3H/HeJ mice

Abstract

The short-term effects of the immunosuppressive drug cyclophosphamide (Cy) are well-documented, but the long-term consequences are not as well studied. Here we report on the kinetics of leukocyte number and immune function recovery following a single intraperitoneal injection of 100 mg/kg or 300 mg/kg Cy. The leukocyte number in spleen, lymph node, bone marrow and thymus was unchanged in C3H/HeJ mice injected with the lower dose of Cy, and was severely but transiently depressed in mice injected with 300 mg/kg Cy. Recovery was complete by day 21. Humoral immunity was unchanged with the lower dose of Cy; mice injected with 300 mg/kg recovered normal antibody production after 3–5 weeks. Natural killer cell function was also transiently depressed in animals receiving the higher but not the lower concentration of Cy. Surprisingly, splenic mitogen responses were markedly inhibited in mice injected with either concentration of Cy. The T-cell proliferative response remained depressed even after 5 weeks in mice injected with 300 mg/kg Cy. Lymphocyte subpopulations in spleen were examined by flow cytometry, and, although some deviations were observed, it is unlikely that these changes are responsible for the highly depressed mitogen response. Thus, there is a loss of the proliferative response to mitogens in Cy-treated mice long after recovery of other lymphocyte functions.