Recombinant granulocyte colony-stimulating factor (G-CSF) was administered to healthy young (n = 32) and elderly (n = 19) volunteers (0 microgram/d, 30 microgram/d, or 300 microgram/d) to determine its effect on neutrophil production, blood kinetics, and tissue migration. Measurements included blood counts (daily), marrow neutrophil pool sizes and neutrophil tissue migration (baseline and day 5), blood kinetics (day 6), and marrow transit time while on drug (days 6 to 14). G-CSF markedly expanded the marrow neutrophil mitotic pool and shortened the transit time of the postmitotic pool (control, mean = 6.4 days; 300 microgram/d, mean = 2.9 d). G-CSF increased neutrophil production without significantly altering blood neutrophil half-life or margination. Compared to control, neutrophil accumulation in skin chambers decreased by about 50% in the 300 microgram/d group in both young and elderly subjects. G-CSF induced neutrophilia by stimulating proliferation of marrow neutrophil precursors and accelerating neutrophil entry into the blood. Decreased neutrophil inflammatory responses measured with the skin chamber technique may be because of the relative immaturity of the circulating cells or to alterations in neutrophil phenotype induced by G-CSF.
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.
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