title: Continuous subcutaneous injection reduces polymorphonuclear leukocyte activation by granulocyte colony-stimulating factor.
abstract: The use of granulocyte colony stimulating factor (G-CSF) for recovery from neutropenia has been established; however, acute lung injury due to G-CSF-induced polymorphonuclear leukocyte (PMN) activation is a serious complication. This study was designed to compare the activation of PMN with single bolus administration and continuous administration of G-CSF. Healthy volunteers (age 33.8 +/- 1.4 yr; n = 6) received a single bolus injection of 50 microm/m2 of G-CSF (SI; n = 6) or continuous subcutaneous injection of 50 microm/m2 of G-CSF for 24 h (CI; n = 6) and were followed for 48 h. Circulating leukocyte counts, markers of activation on PMN, and circulating levels of G-CSF, IL-6, and PMN elastase were measured. SI rapidly increased serum G-CSF levels, which peaked at 4 h, whereas CI gradually increased G-CSF levels, which remained at a steady level from 8 to 24 h. SI caused a rapid decrease in PMN counts at 0.5 h followed by sustained increase to peak at 12 h. CI gradually increased PMN counts, which peaked at 24 h, but the peak values were not significantly different between the groups. SI-induced activation of PMN, which was characterized by increased expression of CD11b, decreased expression of L-selectin, and increased F-actin content, led to increases in serum IL-6 and PMN elastase level. Such changes were all attenuated with CI (P < 0.05). We conclude that continuous subcutaneous injection of G-CSF resulted in a marrow response similar to that to a single injection but yielded reduced PMN activation.
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Jichi Medical School, 3311-1 Minamikawachi, Kawachi, Tochigi 329-0498, Japan. tcvysato@jichi.ac.jp
authors.forename: Yukio
authors.initials: Y
authors.lastname: Sato
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Goto
authors.forename: Shoko
authors.initials: S
authors.lastname: Sato
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Endo
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sohara
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000378:metabolism; D007958:Leukocyte Count; D019272:Leukocyte Elastase / Q000378:metabolism; D008168:Lung / Q000276:immunology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D015850:Interleukin-6; D016179:Granulocyte Colony-Stimulating Factor; D019272:Leukocyte Elastase