Abstract
We examined the in vivo effects of recombinant human granulocyte colony- stimulating factor (rhG-CSF) in primates (cynomolgus monkeys) treated with subcutaneous doses of rhG-CSF for 14-28 d. A dose-dependent increase in the peripheral white blood cells (WBC) was seen, reaching a plateau after 1 wk of rhG-CSF treatment. The elevation of WBC was due to an increase in the absolute neutrophil count. These results demonstrate that rhG-CSF is a potent granulopoietic growth and differentiation factor in vivo. In cyclophosphamide (CY)-induced myelosuppression, rhG-CSF was able to shorten the time period of WBC recovery in two treated monkeys to 1 wk, as compared to more than 4 wk for the control monkey. Its ability to significantly shorten the period of chemotherapy-induced bone marrow hypoplasia may allow clinicians to increase the frequency or dosage of chemotherapeutic agents. In addition, the increase in absolute numbers of functionally active neutrophils may have a profound effect in the rate and severity of neutropenia-related sepsis. Furthermore, the activities reported here indicate a potential role for rhG-CSF in the treatment of patients with myelodysplastic syndrome, congenital agranulocytosis, radiation-induced myelosuppression, and bone marrow transplantation.
Full Text
The Full Text of this article is available as a PDF (569.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BOYDEN S. The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leucocytes. J Exp Med. 1962 Mar 1;115:453–466. doi: 10.1084/jem.115.3.453. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gifford R. H., Malawista S. E. A simple rapid micromethod for detecting chronic granulomatous disease of childhood. J Lab Clin Med. 1970 Mar;75(3):511–519. [PubMed] [Google Scholar]
- Platzer E., Oez S., Welte K., Sendler A., Gabrilove J. L., Mertelsmann R., Moore M. A., Kalden J. R. Human pluripotent hemopoietic colony stimulating factor: activities on human and murine cells. Immunobiology. 1986 Sep;172(3-5):185–193. doi: 10.1016/S0171-2985(86)80098-5. [DOI] [PubMed] [Google Scholar]
- Platzer E., Welte K., Gabrilove J. L., Lu L., Harris P., Mertelsmann R., Moore M. A. Biological activities of a human pluripotent hemopoietic colony stimulating factor on normal and leukemic cells. J Exp Med. 1985 Dec 1;162(6):1788–1801. doi: 10.1084/jem.162.6.1788. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas E. L., Grisham M. B., Jefferson M. M. Myeloperoxidase-dependent effect of amines on functions of isolated neutrophils. J Clin Invest. 1983 Aug;72(2):441–454. doi: 10.1172/JCI110992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Welte K., Platzer E., Lu L., Gabrilove J. L., Levi E., Mertelsmann R., Moore M. A. Purification and biochemical characterization of human pluripotent hematopoietic colony-stimulating factor. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1526–1530. doi: 10.1073/pnas.82.5.1526. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zsebo K. M., Cohen A. M., Murdock D. C., Boone T. C., Inoue H., Chazin V. R., Hines D., Souza L. M. Recombinant human granulocyte colony stimulating factor: molecular and biological characterization. Immunobiology. 1986 Sep;172(3-5):175–184. doi: 10.1016/S0171-2985(86)80097-3. [DOI] [PubMed] [Google Scholar]