title: Cyclophosphamide-induced alterations in human monocyte functions.
abstract: This investigation was designed to study the effects of relatively low doses of cyclophosphamide (CY) on monocyte function in patients with surgically resected melanoma. Monocytes taken from patients 3 days after receiving 300 mg, 150 mg, or 75 mg CY/m2 had decreased interleukin-1 (IL-1) production. Production of tumor necrosis factor (TNF)-like molecules by the same monocytes appeared to be enhanced following 300 mg/m2 CY but not after 150 or 75 mg/m2 CY. In vitro studies of the direct effects of CY metabolites (mafosfamide and 4-hydroperoxycyclophosphamide) on human monocytes showed only concomitant decreases in production of IL-1 and TNF-like molecules. This occurred at concentrations that did not obviously affect viability, although monocyte spreading was inhibited. No evidence was obtained for in vitro enhancement of TNF-production. We conclude that CY can affect monocyte function. In vivo it may have both direct effects leading to decreased TNF and IL-1 production and indirect effects through lymphocytic or haematopoietic systems that activate monocytes to enhanced TNF production. The effects are dose-dependent. These CY-induced changes could be responsible in part for some of the alterations in host immunity and tumor resistance that follows administration of the drug.
mesh_terms: D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007375:Interleukin-1 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014611:Vaccination
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; C048341:mafosfamide; D003520:Cyclophosphamide; C011272:perfosfamide