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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1993 May;92(2):218–224. doi: 10.1111/j.1365-2249.1993.tb03383.x

Therapeutic effect of granulocyte colony-stimulating factor and cephem antibiotics against experimental infections in neutropenic mice induced by cyclophosphamide.

H Wakiyama 1, S Tsuru 1, N Hata 1, M Shinomiya 1, N Shinomiya 1, M Noritake 1, Y Umezawa 1, M Rokutanda 1
PMCID: PMC1554799  PMID: 7683585

Abstract

Effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) against severe infections in cyclophosphamide (CY)-induced neutropenic mice were investigated by its single use or by its combination with cephem antibiotics. Treatment with rhG-CSF increased the number of peripheral blood leucocytes and strikingly shortened the duration of the neutropenic state. Most of the regained population in the peripheral blood leucocytes were neutrophils. Functions of neutrophils, such as phagocytic activity, superoxide release, and expression of Mac-1 molecules, were remarkably enhanced by administration of rhG-CSF. When rhG-CSF was administered to CY-induced neutropenic mice before infection, protective effects against various kinds of bacteria were remarkable. On the other hand, such remarkable effects were not observed when rhG-CSF was administered after infections. However, even in the case of post-infectious treatment, a combination therapy of rhG-CSF with cephem antibiotics, particularly with Cefodizime (CDZM), showed a significant improvement in the survival rate and a decrease in the number of viable bacteria in the liver. These results suggest that a combination therapy of rhG-CSF with cephem antibiotics, especially with CDZM, is an efficient regime against severe infections in patients with neutropenia induced by a heavy anti-tumour chemotherapy.

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Selected References

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  1. Asano S., Ono M. Human granulocyte colony-stimulating factor: its biological actions and clinical implication. Nihon Ketsueki Gakkai Zasshi. 1987 Dec;50(8):1550–1556. [PubMed] [Google Scholar]
  2. Bass D. A., Parce J. W., Dechatelet L. R., Szejda P., Seeds M. C., Thomas M. Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. J Immunol. 1983 Apr;130(4):1910–1917. [PubMed] [Google Scholar]
  3. Burgess A. W., Metcalf D. The nature and action of granulocyte-macrophage colony stimulating factors. Blood. 1980 Dec;56(6):947–958. [PubMed] [Google Scholar]
  4. Clark S. C., Kamen R. The human hematopoietic colony-stimulating factors. Science. 1987 Jun 5;236(4806):1229–1237. doi: 10.1126/science.3296190. [DOI] [PubMed] [Google Scholar]
  5. Cohen A. M., Zsebo K. M., Inoue H., Hines D., Boone T. C., Chazin V. R., Tsai L., Ritch T., Souza L. M. In vivo stimulation of granulopoiesis by recombinant human granulocyte colony-stimulating factor. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2484–2488. doi: 10.1073/pnas.84.8.2484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kitagawa S., Yuo A., Souza L. M., Saito M., Miura Y., Takaku F. Recombinant human granulocyte colony-stimulating factor enhances superoxide release in human granulocytes stimulated by the chemotactic peptide. Biochem Biophys Res Commun. 1987 May 14;144(3):1143–1146. doi: 10.1016/0006-291x(87)91430-6. [DOI] [PubMed] [Google Scholar]
  7. Metcalf D. The granulocyte-macrophage colony-stimulating factors. Science. 1985 Jul 5;229(4708):16–22. doi: 10.1126/science.2990035. [DOI] [PubMed] [Google Scholar]
  8. Nagata S., Tsuchiya M., Asano S., Kaziro Y., Yamazaki T., Yamamoto O., Hirata Y., Kubota N., Oheda M., Nomura H. Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. 1986 Jan 30-Feb 5Nature. 319(6052):415–418. doi: 10.1038/319415a0. [DOI] [PubMed] [Google Scholar]
  9. Nagata S., Tsuchiya M., Asano S., Yamamoto O., Hirata Y., Kubota N., Oheda M., Nomura H., Yamazaki T. The chromosomal gene structure and two mRNAs for human granulocyte colony-stimulating factor. EMBO J. 1986 Mar;5(3):575–581. doi: 10.1002/j.1460-2075.1986.tb04249.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Pierson C. L., Johnson A. G., Feller I. Effect of cyclophosphamide on the immune response to Pseudomonas aeruginosa in mice. Infect Immun. 1976 Jul;14(1):168–177. doi: 10.1128/iai.14.1.168-177.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Sheridan W. P., Morstyn G., Wolf M., Dodds A., Lusk J., Maher D., Layton J. E., Green M. D., Souza L., Fox R. M. Granulocyte colony-stimulating factor and neutrophil recovery after high-dose chemotherapy and autologous bone marrow transplantation. Lancet. 1989 Oct 14;2(8668):891–895. doi: 10.1016/s0140-6736(89)91552-3. [DOI] [PubMed] [Google Scholar]
  12. Shinomiya N., Tsuru S., Katsura Y., Kayashima S., Nomoto K. Enhanced resistance against Listeria monocytogenes achieved by pretreatment with granulocyte colony-stimulating factor. Infect Immun. 1991 Dec;59(12):4740–4743. doi: 10.1128/iai.59.12.4740-4743.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Shinomiya N., Tsuru S., Katsura Y., Noritake M., Shimazaki H., Rokutanda M. [Flow cytometric analysis of oxidative burst of phagocytes with small amount of peripheral blood]. Nihon Saikingaku Zasshi. 1990 Nov;45(6):921–929. doi: 10.3412/jsb.45.921. [DOI] [PubMed] [Google Scholar]
  14. 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. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science. 1986 Apr 4;232(4746):61–65. doi: 10.1126/science.2420009. [DOI] [PubMed] [Google Scholar]
  15. Ulich T. R., del Castillo J., Souza L. Kinetics and mechanisms of recombinant human granulocyte-colony stimulating factor-induced neutrophilia. Am J Pathol. 1988 Dec;133(3):630–638. [PMC free article] [PubMed] [Google Scholar]
  16. Welte K., Bonilla M. A., Gillio A. P., Boone T. C., Potter G. K., Gabrilove J. L., Moore M. A., O'Reilly R. J., Souza L. M. Recombinant human granulocyte colony-stimulating factor. Effects on hematopoiesis in normal and cyclophosphamide-treated primates. J Exp Med. 1987 Apr 1;165(4):941–948. doi: 10.1084/jem.165.4.941. [DOI] [PMC free article] [PubMed] [Google Scholar]

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