Effect of recombinant granulocyte/macrophage colony-stimulating factor on human monocyte activity in vitro and following intravenous administration.
The purpose of these studies was to examine the antitumor properties of blood monocytes from patients undergoing a phase I trial with recombinant granulocyte/macrophage colony-stimulating factor (rGM-CSF). Peripheral blood monocytes from 7 patients receiving various doses of rGM-CSF by continuous infusion were isolated prior to therapy and at various times during the 2-wk infusion. Monocytes/cubic centimeter of blood increased in a dose-dependent fashion in patients receiving rGM-CSF. However, activation of monocyte-mediated tumorilytic properties was seen in only 1 of 7 patients. rGM-CSF administration also did not stimulate interleukin-1 or tumor necrosis factor production by blood monocytes. The failure to detect monocyte-mediated tumoricidal activation was not secondary to an inherent "defect" in the patients' monocytes because in vitro incubation with lipopolysaccharide alone or human recombinant gamma-interferon plus muramyl dipeptide resulted in monocyte-mediated cytotoxicity and in the secretion of interleukin-1 and tumor necrosis factor. rGM-CSF in vitro also did not stimulate the tumoricidal function of normal monocytes or the secretion of interleukin-1 or tumor necrosis factor. We concluded that systemic administration of rGM-CSF did not result in routine activation of monocyte-mediated cytotoxicity but did result in a dose-dependent rise in the number of circulating monocytes. Because these monocytes could be activated in vitro, we propose that, in an adjuvant therapy setting, rGM-CSF be combined with other activating agents to increase the pool of potential killer cells.
D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology* / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009369:Neoplasms / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor