Cyclophosphamide suppression of established cell mediated immunity. Quantitative vs. qualitative changes in lymphocyte populations

Abstract

The characteristics of cyclophosphamide induced suppression of established cell mediated immunity were studied in guinea pigs previously sensitized to tuberculin. Cyclophosphamide treatment for 5 days produced a dose dependent peripheral lymphocytopenia and a disproportionately greater neutropenia which was particularly striking at high doses of 20 mg/kg per day (approximately 200 mg/m2 per day). Lymphocytes remaining in the circulation of cyclophosphamide treated animals showed a dose dependent reduction of both in vitro proliferative and macrophage migration inhibitory factor responses to tuberculin compared to lymphocyte responses of controls. Proliferative responses to phytohemagglutinin and concanavalin A were not significantly suppressed. Additional studies showed that cyclophosphamide suppressed the proliferative and migration inhibitory factor responses to tuberculin of lymph node and splenic as well as circulating lymphocyte populations. These studies showed that relatively short term cyclophosphamide administration produced immunosuppression by quantitative as well as qualitative changes in lymphocyte populations. Significant suppression of lymphocyte function, however, was achieved only with doses of cyclophosphamide which also produced a severe neutropenia.