Quantitative and qualitative effects of cyclophosphamide administration on circulating polymorphonuclear leucocytes

Abstract

The effect of cyclophosphamide (CY) on the absolute numbers and function of polymorphonuclear leucocytes (PMN) surviving in the circulation following either a single dose (100 mg/kg, i.p.) or daily administration (20 mg/kg, i.p., for 5 days) was studied in the guinea-pig. The quantitative effect of CY on peripheral blood leucocytes was assessed by measuring the absolute numbers of neutrophils, lymphocytes, and monocytes daily for 5 days following the initial injection of CY. The qualitative effects of CY on PMN function were determined by measuring the ability of these cells to function as killer cells. The two functional assays employed were the PMN-mediated PHA-induced cellular cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) assays against chicken erythrocyte targets. Both regimens of CY administration produced an equivalent degree of leukopenia 5 days after the initial injection with disproportionately severe neutropenia (less than 300 PMN/mm3). However, neither regimen of CY administration produced a significant decrease in cytotoxic effector function as measured through a wide range of effector to target cell ratios, PHA concentrations, and antiserum dilutions. These findings have clinical relevance in that they demonstrate the dichotomy between the quantitative and qualitative effects of (CY) on PMNs in that CY administration can dramatically decrease the absolute numbers of circulating polymorphonuclear leucocytes while leaving intact certain effector cell functional capabilities of those PMN surviving in the circulation during drug administration.