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Effects of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) on neutrophil kinetics and function in normal human volunteers
Author(s) -
Dale David C.,
Liles W. Conrad,
Llewellyn Claire,
Price Thomas H.
Publication year - 1998
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/(sici)1096-8652(199801)57:1<7::aid-ajh2>3.0.co;2-0
Subject(s) - neutrophilia , medicine , absolute neutrophil count , granulocyte , respiratory burst , granulocyte macrophage colony stimulating factor , endocrinology , granulocyte colony stimulating factor , immunology , eosinophilia , andrology , cytokine , toxicity , chemotherapy , neutropenia
Granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) (250 μg/m 2 ) was administered subcutaneously to 7 normal volunteers for up to 14 days to study its effects on neutrophil kinetics and function. With treatment, blood neutrophil counts rose gradually to peak at 3½ times baseline by day 14. At day 5 marrow mitotic cells were increased and post‐mitotic cells decreased, and the transit time through the post‐mitotic marrow pool accelerated (normal = 6.4 days, GM‐CSF = 3.9 days; P < 0.01). Treatment had little effect on the blood neutrophil half‐life (normal = 9.6 ± 1.3 hours; GM‐CSF = 13.1 ± 2.4 hours, P > 0.05); or the neutrophil turnover rate (normal = 78.5 ± 11.9 × 10 7 /cells/kg/day, GM‐CSF = 91.4 ± 19.8 × 10 7 /cells/kg/day, P > 0.05). GM‐CSF reduced the number of neutrophils migrating to skin chambers (normal = 104 ± 25.0 × 10 6 /cells, GM‐CSF = 48.6 ± 16.0 × 10 6 /cells; P < 0.05). Treatment increased expression of CD11b/CD18 but not Fcγ receptors (CD16, CD32, CD64). Treatment also stimulated the in vitro neutrophil respiratory burst in response to a variety of agonists, and this enhancement persisted for the duration of treatment. All subjects experienced local and systemic adverse effects and developed eosinophilia. This study indicates that GM‐CSF at a dose of 250 μg/m 2 causes neutrophilia chiefly by accelerating delivery of neutrophils from the marrow to the blood and by decreasing migration from the blood to the tissues, with only a modest effect on neutrophil production and blood half‐life. Am. J. Hematol. 57:7–15, 1998. © 1998 Wiley‐Liss, Inc.