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G-CSF prevents the suppression of bone marrow hematopoiesis induced by IL-12 and augments its antitumor activity in a melanoma model in mice.
- Source :
-
Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 1998 Jan; Vol. 9 (1), pp. 63-9. - Publication Year :
- 1998
-
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.<br />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 C-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.<br />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 melanoma model. The augmented antitumor activity of combined IL-12/G-CSF immunotherapy could result from the enhanced stimulation of macrophage NO production and cytotoxicity.<br />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.
- Subjects :
- Animals
Disease Models, Animal
Drug Interactions
Interleukin-12 antagonists & inhibitors
Leukocyte Count drug effects
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Nitric Oxide biosynthesis
Recombinant Proteins therapeutic use
Spleen drug effects
Antineoplastic Agents therapeutic use
Bone Marrow drug effects
Granulocyte Colony-Stimulating Factor therapeutic use
Hematopoiesis drug effects
Interleukin-12 therapeutic use
Melanoma, Experimental drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0923-7534
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Annals of oncology : official journal of the European Society for Medical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 9541685
- Full Text :
- https://doi.org/10.1023/a:1008266321552