Effects of continuous high dose rhgm‐csf infusion on human monocyte activity

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Abstract
In this study we describe the time‐dependent effects of a high dose (750 (μg/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 × 105 on day 0 to 21 × 105 on day 14 of infusion. There was no significant change in the basal release of tumor necrosis factor α (TNF‐α) or interleukin 1β (IL‐1β) induced by rhGM‐CSF. However, the lipopolysaccharide (LPS)‐stimulated release of TNF‐α by monocytes increased significantly on day 1 of infusion, and by day 14 had increased 8‐fold. IL‐1β 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‐α and IL‐1β, and superoxide anion production from these monocytes. These primed monocytes could enhance the ability of neutropenic patients to fight infection.

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