Effects of in vivo recombinant methionyl human granulocyte colony-stimulating factor on the neutrophil response and peripheral blood colony-forming cells in healthy young and elderly adult volunteers.

Recombinant granulocyte colony stimulating factor (G-CSF) was administered daily for 14 days to healthy young (Y) (20 to 30 years) and elderly (O) (70 to 80 years) volunteers to evaluate the effects of age on the neutrophil (polymorphonuclear leukocytes, PMN) responses. Thirty-eight volunteers were randomized to receive 0 micrograms, 30 micrograms, or 300 micrograms per day. Baseline neutrophil counts (ANC), peak ANCs, and the rate of attaining the peak ANC were similar in both age groups at both doses. The peak ANC was increased 5-fold at 30 micrograms and 15-fold at 300 micrograms in both the young and elderly. Daily tests of PMN function, as measured by an automated chemiluminescence system, showed nearly identical responses to several agonists for both age groups. Marrow proliferative activity as reflected by the percentage of cells in the marrow neutrophil mitotic pool also increased similarly for both age groups at both doses. In contrast, there was an age-related change in blood colony formation as measured by the blood CFU-GM assay. Compared with controls at the 30 micrograms dose, mean colony formation was increased 2-fold in the young versus no change in the elderly and at the 300 micrograms dose 24-fold in the young versus 12-fold in the elderly. These studies indicate that neutrophil responses to rhG-CSF are equivalent in healthy young and elderly volunteers but the mobilization of progenitor cells, as measured by the CFU-GM assay appears to differ substantially.

[1]  G. Demetri,et al.  Granulocyte colony-stimulating factor and its receptor. , 1991, Blood.

[2]  G. Chatta,et al.  Hematopoietic progenitors and aging: alterations in granulocytic precursors and responsiveness to recombinant human G-CSF, GM-CSF, and IL-3. , 1993, Journal of gerontology.

[3]  R. Larson,et al.  Structure and Function of Leukocyte Integrins , 1990, Immunological reviews.

[4]  G. Morstyn,et al.  The role of granulocyte colony-stimulating factor in cancer chemotherapy. , 1991, Seminars in hematology.

[5]  R. Christensen,et al.  Kinetic evaluation of the pool sizes and proliferative response of neutrophils in bacterially challenged aging mice. , 1987, Blood.

[6]  P. Laharrague,et al.  Polymorphonuclear Functions and Aging in Humans * , 1981, Journal of the American Geriatrics Society.

[7]  C. Begg,et al.  Clinical trials and drug toxicity in the elderly. The experience of the eastern cooperative oncology group , 1983, Cancer.

[8]  D. Crowther,et al.  In vitro and in vivo analysis of the effects of recombinant human granulocyte colony-stimulating factor in patients. , 1988, British Journal of Cancer.

[9]  Michael D. Green,et al.  GRANULOCYTE COLONY-STIMULATING FACTOR AND NEUTROPHIL RECOVERY AFTER HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS BONE MARROW TRANSPLANTATION , 1989, The Lancet.

[10]  K. Zsebo,et al.  In vivo stimulation of granulopoiesis by recombinant human granulocyte colony-stimulating factor. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Akiko Tanaka,et al.  Hematopoietic stem cells in elderly people , 1986, Mechanisms of Ageing and Development.

[12]  J. Gabrilove,et al.  Phase I study of granulocyte colony-stimulating factor in patients with transitional cell carcinoma of the urothelium. , 1988, The Journal of clinical investigation.

[13]  G. Chatta,et al.  Aging and Marrow Neutrophil Reserves , 1994, Journal of the American Geriatrics Society.

[14]  M. Kris,et al.  Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. , 1994, The New England journal of medicine.

[15]  J. Villeval,et al.  Effects of recombinant human granulocyte colony-stimulating factor on hematopoietic progenitor cells in cancer patients. , 1988, Blood.

[16]  T. Murphy,et al.  Bacteremic Pneumococcal Pneumonia in the Elderly , 1984, The American journal of the medical sciences.

[17]  J. Baldwin Hematopoietic function in the elderly. , 1988, Archives of internal medicine.

[18]  M. Weksler,et al.  Immunological studies of aging. Decreased production of and response to T cell growth factor by lymphocytes from aged humans. , 1981, The Journal of clinical investigation.

[19]  R. Allen Phagocytic leukocyte oxygenation activities and chemiluminescence: a kinetic approach to analysis. , 1986, Methods in enzymology.

[20]  J. Cream Prednisolone‐Induced Granulocytosis , 1968, British journal of haematology.

[21]  M. Timaffy A comparative study of bone marrow function in young and old individuals. , 1962, Gerontologia clinica.

[22]  L. Balducci,et al.  Recombinant Hemopoietic Growth Factors: Comparative Hemopoietic Response in Younger and Older Subjects , 1992, Journal of the American Geriatrics Society.

[23]  K. Udupa,et al.  Effect of age on hematopoiesis in man. , 1984, Blood.

[24]  H. Malech,et al.  Recombinant human stem cell factor enhances myeloid colony growth from human peripheral blood progenitors. , 1993, Blood.

[25]  G. Rothstein Hematopoiesis in the aged: a model of hematopoietic dysregulation? [editorial; comment] , 1993 .

[26]  G. Rothstein Hematopoiesis in the aged: a model of hematopoietic dysregulation? , 1993, Blood.

[27]  M. Green,et al.  Treatment of chemotherapy-induced neutropenia by subcutaneously administered granulocyte colony-stimulating factor with optimization of dose and duration of therapy. , 1989, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  P. Peterson,et al.  Immunodeficiency of the elderly. , 1987, Reviews of infectious diseases.

[29]  J. Gabrilove,et al.  Effect of Granulocyte Colony-Stimulating Factor on Neutropenia and Associated Morbidity Due to Chemotherapy for Transitional-Cell Carcinoma of the Urothelium , 1989 .

[30]  R. Macgregor,et al.  Neutrophil function in healthy elderly subjects. , 1990, Journal of gerontology.

[31]  R. Allen,et al.  The circulating phagocyte reflects the in vivo state of immune defense , 1992 .

[32]  D. Boggs,et al.  In vitro growth of granulocytic and mononuclear cell colonies from blood of normal individuals. , 1971, Blood.

[33]  G D Long,et al.  Granulocyte colony-stimulating factor "mobilized" peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high-dose chemotherapy. , 1993, Blood.

[34]  S. Hellman,et al.  Decline in bone marrow proliferative capacity as a function of age. , 1982, Blood.

[35]  G. Chatta,et al.  Abnormal responsiveness of granulocyte-committed progenitor cells in cyclic neutropenia. , 1992, Blood.