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Related Experiment Videos

Cyclophosphamide-induced alterations in human monocyte functions.

W H McBride1, D B Hoon, T Jung

  • 1Department of Radiation Oncology, University of California, Los Angeles 90024.

Journal of Leukocyte Biology
|December 1, 1987
PubMed
Summary

Low doses of cyclophosphamide (CY) impact monocyte function, decreasing interleukin-1 (IL-1) and potentially enhancing tumor necrosis factor (TNF) production in melanoma patients. These dose-dependent effects influence host immunity and tumor resistance.

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Area of Science:

  • Immunology
  • Pharmacology
  • Oncology

Background:

  • Cyclophosphamide (CY) is an alkylating agent used in cancer therapy.
  • Its effects on immune cells, particularly monocytes, are not fully understood at low therapeutic doses.
  • Melanoma patients undergoing surgical resection are often treated with chemotherapy, including CY.

Purpose of the Study:

  • To investigate the impact of low-dose cyclophosphamide (CY) on human monocyte function.
  • To differentiate between in vivo and in vitro effects of CY and its metabolites on cytokine production.
  • To explore the dose-dependent relationship between CY administration and monocyte activity.

Main Methods:

  • Monocytes were isolated from melanoma patients 3 days post-CY administration (75, 150, 300 mg/m2).

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  • Interleukin-1 (IL-1) and tumor necrosis factor (TNF)-like molecule production were measured.
  • In vitro studies assessed direct effects of CY metabolites (mafosfamide, 4-hydroperoxycyclophosphamide) on monocyte viability, spreading, IL-1, and TNF production.

    • Main Results:

    • In vivo, CY administration led to decreased IL-1 production across all doses.
    • Enhanced TNF-like molecule production was observed only at the highest CY dose (300 mg/m2).
    • In vitro, CY metabolites reduced both IL-1 and TNF production without significant impact on cell viability, though monocyte spreading was inhibited.

    Conclusions:

    • Cyclophosphamide significantly affects monocyte function in a dose-dependent manner.
    • In vivo effects include decreased IL-1 and potentially enhanced TNF production, possibly mediated by indirect mechanisms.
    • In vitro data suggest direct inhibitory effects of CY metabolites on monocyte cytokine production.