Abstract
The effect of co‐administration of granulocyte colony‐stimulating factor (G‐CSF), as an anti‐neutropenia agent, on interferon therapy was examined in a mouse model, in anticipation of an enhancement of interferon efficacy, because neutrophils induced by G‐CSF are thought to act as antitumor effectors. G‐CSF was intraperitoneally co‐administered with human interferon α A/D (IFN) on Day 6 to Day 10 after intradermal inoculation of Meth A fibrosarcoma. Although the co‐administration of G‐CSF could protect against neutropenia and leukopenia induced by IFN, it did not enhance the regression of tumor, and rather reduced the prolongation of survival time and the long‐term survival incidence of IFN therapy. The subsequent in vitro study showed that the antiproliferative activity of peripheral blood leukocytes from Meth A‐bearing mice given both IFN and G‐CSF was much weaker than that of mice given IFN alone. Whether the observed nullifying effect of G‐CSF on IFN therapy is also the case with tumors other than Meth A is open to further study.
Keywords: Interferon α A/D, Granulocyte colony‐stimulating factor, Monocyte, Immunosuppression, Meth A fibrosarcoma
Full Text
The Full Text of this article is available as a PDF (299.7 KB).
REFERENCES
- 1. ) Honjo , K. , Suhara , Y. , Taniyama , T. and Kataoka , T.Production of antitumor mononuclear blood cells in tumor‐bearing mice by interferon‐αA/D therapy . J. Interferon Res. , 10 , 191 – 202 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Fujii , Y. , Kimura , S. , Arai , S. and Sendo , F.In vivo antitumor effect of lymphokine‐activated rodent polymorphonuclear leukocytes . Cancer Res. , 47 , 6000 – 6005 ( 1987. ). [PubMed] [Google Scholar]
- 3. ) Lichtenstein , A. K. , Kahle , J. , Berek , J. and Zighelboim , J.Successful immunotherapy with intraperitoneal Corynebacterium parvum in a murine ovarian cancer model is associated with the recruitment of tumor‐lytic neutrophils into the peritoneal cavity . J. Immunol. , 133 , 519 – 526 ( 1984. ). [PubMed] [Google Scholar]
- 4. ) Morikawa , K. , Takeda , R. , Yamazaki , M. and Mizuno , D.Induction of tumoricidal activity of polymorphonuclear leukocytes by a linear β‐l,3‐d‐glucan and other immunomodulators in murine cells . Cancer Res. , 45 , 1496 – 1501 ( 1985. ). [PubMed] [Google Scholar]
- 5. ) Rehberg , E. , Kelder , B. , Hoal , E. G. and Pestka , S.Specific molecular activities of recombinant and hybrid leukocyte interferons . J. Biol Chem. , 251 , 11497 – 11502 ( 1982. ). [PubMed] [Google Scholar]
- 6. ) Souza , L. M. , Boone , T. C. , Gabrilove , J. , Lai , P. H. , Zsebo , K. M. , Murdock , D. C. , Chazin , V. R. , Bruszewski , J. , Lu , H. , Chen , K. K. , Barendt , J. , Platzer , E. , Moore , M. A. S. , Mertelsmann , R. and Welte , K.Recombinant human granulocyte colony‐stimulating factor: effects on normal and leukemic myeloid cells . Science , 232 , 61 – 65 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Cohen , A. M. , Zsebo , K. M. , Inoue , H. , Hines , D. , Boone , T. C. , Chazin , V. R. , Tsai , L. , Ritch , T. and Souza , L. M.In vivo stimulation of granulopoiesis by recombinant human granulocyte colony‐stimulating factor . Proc. Natl. Acad. Sci. USA , 84 , 2484 – 2488 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. ) Fujisawa , M. , Kobayashi , Y. , Okabe , T. , Takaku , F. , Komatsu , Y. and Itoh , S.Recombinant human granulocyte colony‐stimulating factor induces granulocytosis in vivo . Jpn. J. Cancer Res. , 77 , 866 – 869 ( 1986. ). [PubMed] [Google Scholar]
- 9. ) Kitagawa , S. , Yuo , A. , Souza , L. M. , Saito , M. , Miura , Y. and Takaku , F.Recombinant human granulocyte colony‐stimulating factor enhances superoxide release in human granulocytes stimulated by the chemotactic peptide . Biochem. Biophys. Res. Commun. , 144 , 1143 – 1146 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 10. ) Yuo , A. , Kitagawa , S. , Okabe , T. , Urabe , A. , Komatsu , Y. , Itoh , S. and Takaku , F.Recombinant human granulocyte colony‐stimulating factor repairs the abnormalities of neutrophils in patients with myelodysplastic syndromes and chronic myelogenous leukemia . Blood , 70 , 404 – 411 ( 1987. ). [PubMed] [Google Scholar]
- 11. ) Bronchud , M. H. , Scarffe , J. H. , Thatcher , N. , Crowther , D. , Souza , L. M. , Alton , N. K. , Testa , N. G. and Dexter , T. M.Phase I/II study of recombinant human granulocyte colony‐stimulating factor in patients receiving intensive chemotherapy for small cell lung cancer . Br. J. Cancer , 56 , 809 – 813 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. ) Kobayashi , Y. , Okabe , T. , Urabe , A. , Suzuki , N. and Takaku , F.Human granulocyte colony‐stimulating factor produced by Escherichia coli shortens the period of granulocytopenia induced by irradiation in mice . Jpn. J. Cancer Res. , 78 , 763 – 766 ( 1987. ). [PubMed] [Google Scholar]
- 13. ) Kay , H. D. and Smith , D. L.Regulation of human lymphocyte‐mediated natural killer (NK) cell activity. I. Inhibition in vitro by peripheral blood granulocytes . J. Immunol. , 130 , 475 – 483 ( 1983. ). [PubMed] [Google Scholar]
- 14. ) Seaman , W. E. , Gindhart , T. D. , Blackman , M. A. , Dalai , B. , Talal , N. and Werb , Z.Suppression of natural killing in vitro by monocytes and polymorphonuclear leukocytes . J. Clin. Invest. , 69 , 876 – 888 ( 1982. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. ) Shau , H. and Kim , A.Suppression of lymphokine‐activated killer induction by neutrophils . J. Immunol. , 141 , 4395 – 4402 ( 1988. ). [PubMed] [Google Scholar]
- 16. ) Shau , H. and Golub S. H.Inhibition of lymphokine‐activated killer‐ and natural killer‐mediated cytotoxicities by neutrophils . J. Immunol. , 143 , 1066 – 1072 ( 1989. ). [PubMed] [Google Scholar]