Recombinant human granulocyte/macrophage colony-stimulating factor enhances monocyte cytotoxicity and secretion of tumor necrosis factor alpha and interferon in cancer patients.
The colony-stimulating factors (CSFs) promote the proliferation and differentiation of hematopoietic precursors and more recently have been shown to amplify the functions of mature phagocytes in vitro. In this study recombinant human granulocyte/macrophage colony-stimulating factor (rGM-CSF) was administered to cancer patients to determine whether the cytotoxic and secretory activity of their blood monocytes could be enhanced. Patients with refractory neoplastic disease were treated with rGM-CSF either as a single bolus or as a constant infusion for 14 days at either 100 or 500 micrograms/m2 per day. As has been reported by others, the number of peripheral blood monocytes and granulocytes rose markedly in a dose-response fashion during infusion with rGM-CSF. The functional capacity of monocytes was increased by rGM-CSF, since the cytotoxicity of monocytes against antibody-coated xenogeneic cells was increased during the constant infusion compared to baseline. In addition, monocytes harvested during the constant infusion and stimulated with lipopolysaccharide (LPS) in vitro secreted increased quantities of tumor necrosis factor alpha (TNF-alpha) and interferon (IFN). These data indicate that rGM-CSF can enhance both the number and the function of peripheral blood monocytes in vivo.
Wing
E J
EJ
Montefiore Hospital, Department of Medicine, University of Pittsburgh School of Medicine, PA 15213.
Magee
D M
DM
Whiteside
T L
TL
Kaplan
S S
SS
Shadduck
R K
RK
D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007372:Interferons / Q000378:metabolism*; D007958:Leukocyte Count; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D012636:Secretory Rate / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007372:Interferons