IMMUNOLOGICAL REACTIVITY OF LUNG .4. EFFECT OF CYCLOPHOSPHAMIDE ON ALVEOLAR MACROPHAGE CYTOTOXIC EFFECTOR FUNCTION

Abstract

The effect of cyclophosphamide (CY) on the absolute numbers and function of alveolar macrophages following in vitro or in vivo drug exposure was studied in the guinea pig. Two separate regimens of in vivo cyclophosphamide administration (100 mg/kg/1 dose or 20 mg/kg for 5 days), both of which produce identical decreases in each population of peripheral blood leukocytes 5 days after the initial injection, did not produce any change in alveolar macrophage numbers when compared to control values. Neither a brief exposure to CY in vitro nor a brief exposure in vivo (100 mg/kg/1 dose) caused any change in cytotoxic effector function of alveolar macrophages using the PHA[phytohemagglutinin]-induced and antibody-dependent cellular cytotoxicity assays against sheep erythrocyte targets. The more prolonged in vivo exposure to CY (20 mg/kg for 5 days), produced a significant decrease in the killer cell function of these cells. Different regimens of CY administration, although producing similar degrees of peripheral blood leukopenia, can produce markedly different effects on the functional capabilities of alveolar macrophages without quantitatively decreasing the absolute numbers of these cells.