G-CSF prevents the suppression of bone marrow hematopoiesis induced by IL-12 and augments is antitumor activity in a melanoma model in mice

J. Gołab, T. Stokłosa, R. Zagozdzon, A. Kaca, Adam Giermasz, Z. Pojda, E. Machaj, A. Dabrowska, W. Feleszko, W. Lasek, A. Iwan-Osiecka, M. Jakóbisiak

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Background: IL-12 has been successfully used in experimental tumor therapy. However, administration of this cytokine induces dose-dependent suppression of hematopoiesis that could potentially limit its use in clinical trials. We decided to examine whether the myelosuppressive activity of IL-12 could be corrected by the administration of G-CSF. Materials and methods: In the initial experiments the influence of IL-12 and/or G-CSF on bone marrow and spleen GM-CFC was evaluated. To examine whether G-CSF could influence the antitumor activity of IL-12 the combination therapy with these agents was carried out starting on day seven following inoculation of melanoma MmB16 cells into the footpads of B6D2F1 mice. To obtain insight into the mechanism of the observed augmented antitumor activity of the combination therapy with IL-12 and G-CSF, the influence of these cytokines on macrophage activity (cytotoxicity and nitric oxide release) was analyzed. Results: In accord with our expectations, the application of G-CSF partially prevented the suppression of bone marrow myelopoiesis in IL-12-treated mice. Unexpectedly, G-CSF also showed potentiation of antitumor effects of IL-12 in this mechanoma model. The augmented antitumor activity of combined IL-12/G-CSF immunotherapy could result from the enhanced stimulation of macrophage NO production and cytotoxicity. Conclusion: The simultaneous administration of IL-12 and G-CSF partially prevented suppression of bone marrow myelopoiesis in IL-12-treated mice. Moreover, treatment with these cytokines also results in potentiated antitumor effects in a murine melanoma model.

Original languageEnglish (US)
Pages (from-to)63-69
Number of pages7
JournalAnnals of Oncology
Volume9
Issue number1
DOIs
StatePublished - Jan 1998
Externally publishedYes

Keywords

  • Granulocyte colony-stimulating factor
  • Interleukin-12
  • Melanoma

ASJC Scopus subject areas

  • Hematology
  • Oncology

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    Gołab, J., Stokłosa, T., Zagozdzon, R., Kaca, A., Giermasz, A., Pojda, Z., Machaj, E., Dabrowska, A., Feleszko, W., Lasek, W., Iwan-Osiecka, A., & Jakóbisiak, M. (1998). G-CSF prevents the suppression of bone marrow hematopoiesis induced by IL-12 and augments is antitumor activity in a melanoma model in mice. Annals of Oncology, 9(1), 63-69. https://doi.org/10.1023/A:1008266321552