Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1976 Jul;31(1):139–144.

Quantitative and qualitative effects of cyclophosphamide administration on circulating polymorphonuclear leucocytes.

G W Hunninghake, A S Fauci
PMCID: PMC1445100  PMID: 1027718

Abstract

The effect of cyclophosphamide (CY) on the absolute numbers and function of polymorphonuclear leucocytes (PMN) surviving in the circulation following either a single dose (100 mg/kg, i.p.) or daily administration (20 mg/kg, i.p., for 5 days) was studied in the guinea-pig. The quantitative effect of CY on peripheral blood leucocytes was assessed by measuring the absolute numbers of neutrophils, lymphocytes, and monocytes daily for 5 days following the initial injection of CY. The qualitative effects of CY on PMN function were determined by measuring the ability of these cells to function as killer cells. The two functional assays employed were the PMN-mediated PHA-induced cellular cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) assays against chicken erythrocyte targets. Both regimens of CY administration produced an equivalent degree of leukopenia 5 days after the initial injection with disproportionately severe neutropenia (less than 300 PMN/mm3). However, neither regimen of CY administration produced a significant decrease in cytotoxic effector function as measured through a wide range of effector to target cell ratios, PHA concentrations, and antiserum dilutions. These findings have clinical relevance in that they demonstrate the dichotomy between the quantitative and qualitative effects of (CY) on PMNs in that CY administration can dramatically decrease the absolute numbers of circulating polymorphonuclear leucocytes while leaving intact certain effector cell functional capabilities of those PMN surviving in the circulation during drug administration.

Full text

PDF
139

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Atkinson K., Kay H. E., McElwain T. J. Fever in the neutropenic patient. Br Med J. 1974 Jul 20;3(5924):160–161. doi: 10.1136/bmj.3.5924.160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Balow J. E., Hurley D. L., Fauci A. S. Cyclophosphamide suppression of established cell-mediated immunity. Quantitative vs. qualitative changes in lymphocyte populations. J Clin Invest. 1975 Jul;56(1):65–70. doi: 10.1172/JCI108080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dale D. C., Fauci A. S., Wolff S. M. The effect of cyclophosphamide on leukocyte kinetics and susceptibility to infection in patients with Wegener's granulomatosis. Arthritis Rheum. 1973 Sep-Oct;16(5):657–664. doi: 10.1002/art.1780160510. [DOI] [PubMed] [Google Scholar]
  4. Deinard A. S., Fortuny I. E., Theologides A., Anderson G. L., Boen J., Kennedy B. J. Studies on the neutropenia of cancer chemotherapy. Cancer. 1974 May;33(5):1210–1218. doi: 10.1002/1097-0142(197405)33:5<1210::aid-cncr2820330503>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  5. Fauci A. S., Wolff S. M. Wegener's granulomatosis: studies in eighteen patients and a review of the literature. Medicine (Baltimore) 1973 Nov;52(6):535–561. doi: 10.1097/00005792-197311000-00002. [DOI] [PubMed] [Google Scholar]
  6. Freireich E. J., Gehan E. A., Rall D. P., Schmidt L. H., Skipper H. E. Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man. Cancer Chemother Rep. 1966 May;50(4):219–244. [PubMed] [Google Scholar]
  7. Gale R. P., Zighelboim J. Modulation of polymorphonuclear leukocyte-mediated antibody-dependent cellular cytotoxicity. J Immunol. 1974 Dec;113(6):1793–1800. [PubMed] [Google Scholar]
  8. Gale R. P., Zighelboim J. Polymorphonuclear leukocytes in antibody-dependent cellular cytotoxicity. J Immunol. 1975 Mar;114(3):1047–1051. [PubMed] [Google Scholar]
  9. Gershwin M. E., Goetzl E. J., Steinberg A. D. Cyclophosphamide: use in practice. Ann Intern Med. 1974 Apr;80(4):531–540. doi: 10.7326/0003-4819-80-4-531. [DOI] [PubMed] [Google Scholar]
  10. Holley T. R., Van Epps D. E., Harvey R. L., Anderson R. E., Williams R. C., Jr Effect of high doses of radiation on human neutrophil chemotaxis, phagocytosis and morphology. Am J Pathol. 1974 Apr;75(1):61–72. [PMC free article] [PubMed] [Google Scholar]
  11. Kirchner H., Blaese R. M. Pokeweed mitogen-, concanavalin A-, and phytohemagglutinin-induced development of cytotoxic effector lymphocytes. An evaluation of the mechanisms of T cell-mediated cytotoxicity. J Exp Med. 1973 Oct 1;138(4):812–824. doi: 10.1084/jem.138.4.812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Klebanoff S. J. Antimicrobial mechanisms in neutrophilic polymorphonuclear leukocytes. Semin Hematol. 1975 Apr;12(2):117–142. [PubMed] [Google Scholar]
  13. Levine A. S., Graw R. G., Jr, Young R. C. Management of infections in patients with leukemia and lymphoma: current concepts and experimental approaches. Semin Hematol. 1972 Apr;9(2):141–179. [PubMed] [Google Scholar]
  14. Miller M. E. Pathology of chemotaxis and random mobility. Semin Hematol. 1975 Jan;12(1):59–82. [PubMed] [Google Scholar]
  15. Perlmann P., Holm G. Cytotoxic effects of lymphoid cells in vitro. Adv Immunol. 1969;11:117–193. doi: 10.1016/s0065-2776(08)60479-4. [DOI] [PubMed] [Google Scholar]
  16. Perlmann P., Perlmann H. Contactual lysis of antibody-coated chicken erythrocytes by purified lymphocytes. Cell Immunol. 1970 Sep;1(3):300–315. doi: 10.1016/0008-8749(70)90051-1. [DOI] [PubMed] [Google Scholar]
  17. Perlmann P., Perlmann H., Holm G. Cytotoxic action of stimulated lymphocytes on allogenic and autologous erythrocytes. Science. 1968 Apr 19;160(3825):306–309. doi: 10.1126/science.160.3825.306. [DOI] [PubMed] [Google Scholar]
  18. Rodriguez V., Burgess M., Bodey G. P. Management of fever of unknown origin in patients with neoplasms and neutropenia. Cancer. 1973 Oct;32(4):1007–1012. doi: 10.1002/1097-0142(197310)32:4<1007::aid-cncr2820320437>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  19. Stossel T. P. Phagocytosis: recognition and ingestion. Semin Hematol. 1975 Jan;12(1):83–116. [PubMed] [Google Scholar]
  20. Turk J. L., Poulter L. W. Selective depletion of lymphoid tissue by cyclophosphamide. Clin Exp Immunol. 1972 Feb;10(2):285–296. [PMC free article] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES