Effects of continuous high dose rhGM-CSF infusion on human monocyte activity.
In this study we describe the time-dependent effects of a high dose (750 micrograms/ml/24 hr) continuous infusion of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on monocyte number, cytokine release, and superoxide anion production. Blood was taken from patients prior to rhGM-CSF infusion (day 0), and on days 1, 7, and 14 of infusion. The mean concentration of monocytes per ml of blood increased progressively from 4.3 x 10(5) on day 0 to 21 x 10(5) on day 14 of infusion. There was no significant change in the basal release of tumor necrosis factor alpha (TNF-alpha) or interleukin 1 beta (IL-1 beta) induced by rhGM-CSF. However, the lipopolysaccharide (LPS)-stimulated release of TNF-alpha by monocytes increased significantly on day 1 of infusion, and by day 14 had increased 8-fold. IL-1 beta release from LPS-stimulated monocytes increased slightly by day 7, and by almost 10-fold by day 14 of infusion. When maximally stimulated with phorbol dibutyrate, the monocytes demonstrated an increased (although not significant) capacity to produce superoxide anion on days 7 and 14 of infusion. No change in basal superoxide anion production was seen at any day of infusion. These GM-CSF-induced changes in stimulated cytokine and superoxide anion release could not be reproduced by treating monocytes with rhGM-CSF in vitro. In summary, a two week, high dose infusion of rhGM-CSF resulted in increases in circulating monocyte concentration, and in the stimulated release of TNF-alpha and IL-1 beta, and superoxide anion production from these monocytes. These primed monocytes could enhance the ability of neutropenic patients to fight infection.
Perkins
R C
RC
Department of Internal Medicine, University of Texas of Medical School, Houston.
Vadhan-Raj
S
S
Scheule
R K
RK
Hamilton
R
R
Holian
A
A
D000328:Adult; D000704:Analysis of Variance; D001772:Blood Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012509:Sarcoma / Q000378:metabolism / Q000473:pathology; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor