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Cancer Immunology, Immunotherapy

, Volume 52, Issue 7, pp 463–472 | Cite as

Doxorubicin induces specific immune functions and cytokine expression in peritoneal cells

  • Peter Ujhazy
  • Gintaras Zaleskis
  • Enrico Mihich
  • M. Jane Ehrke
  • Erica S. BerlethEmail author
Original Article

Abstract

To examine the basis of the immune modulation induced by the anticancer agent doxorubicin (DOX), the immunophenotype, tumoricidal activity, cytokine protein and mRNA expression were determined using peritoneal exudate cells (PEC) from saline-treated (untreated) and DOX-treated mice. A greater percentage of PEC from DOX-treated mice than from untreated mice were adherent to plastic, had characteristics of granulocytes, and were positive for the NK1.1, CD11b/Mac-1, and CD3 markers. DOX decreased the percentage of CD45R/B220+ cells. PEC from DOX-treated mice had greater tumoricidal potential than those from untreated mice since IL2, LPS, or IFNγ alone increased the cytolytic activity of PEC from DOX-treated mice, whereas PEC from untreated mice required both LPS and IFNγ to become cytolytic. DOX treatment modulated the expression of specific cytokines. Following stimulation in culture, PEC from DOX-treated mice produced more TNF, IL1, and IFNγ than PEC from untreated mice. DOX treatment increased the levels of TNF, but not IL1, mRNA and decreased the levels of IL6 mRNA and protein. These data demonstrate that a single DOX injection induces specific effects in PEC and, as a consequence, increases the tumoricidal potential of cells of the macrophage and natural killer types.

Keywords

Immunomodulation Interleukin NK TNF Tumoricidal macrophage 

Abbreviations

Ad

Adherent

CM

Conditioned media

CTL

Cytolytic T lymphocyte

DOX

Doxorubicin

FSC

Forward scatter

IFNγ

Interferon γ

IL

Interleukin

LAK

Lymphokine-activated killer

LGL

Large granulocytic lymphocyte

LPS

Lipopolysaccharide

MTT

[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]

NAd

Nonadherent

NK

Natural killer cell

PBL

Peripheral blood lymphocyte

PCR

Polymerase chain reaction

PEC

Peritoneal exudate cells

RT

Reverse transcription

SSC

Side scatter

TNF

Tumor necrosis factor α

W

Whole

Notes

Acknowledgements

The authors would like to acknowledge Cheryl Eppolito and Jane Meer for their expert technical assistance. These studies were supported, in part, by NIH NCI grants CA15142 (R01) and CA16056 (center grant).

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Peter Ujhazy
    • 1
    • 2
  • Gintaras Zaleskis
    • 1
    • 3
  • Enrico Mihich
    • 1
  • M. Jane Ehrke
    • 1
  • Erica S. Berleth
    • 1
    Email author
  1. 1.Department of Pharmacology and Therapeutics, Grace Cancer Drug CenterRoswell Park Cancer InstituteBuffaloUSA
  2. 2.Organ Systems Branch, OCTR, ODDESNCIRockvilleUSA
  3. 3.Eksma Medical InstrumentsVilniusLithuania

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