Effect of granulocyte-macrophage colony-stimulating factor treatment on phenotype, cytokine release and cytotoxicity of circulating blood monocytes and monocyte-derived macrophages.
We studied phenotype, function and differentiation of mononuclear phagocytes in 11 cancer patients treated subcutaneously with 10O microg/kg recombinant human (rhu) GM-CSF for 7 d. The rhuGM-CSF treatment induced (1) a 5.9-fold increase in the number of blood monocytes (MO), (2) a decrease of CD14bright/CD16bright cells with a diminution of the mean fluorescence intensity (MFI) of CD14, and (3) a decrease of MO cellular cytotoxicity. In patients' sera, tumour necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-12, neopterin, macrophage-colony-stimulating factor (M-CSF), and IL-1 receptor antagonist (IL-1RA) increased, whereas GM-CSF and granulocyte-colony-stimulating factor (G-CSF) decreased after an initial peak. In whole blood samples the lipopolysaccharide (LPS)-stimulated release of TNF-alpha, IL-6 and IL-1RA increased initially, whereas IL-1beta, IL-10 and IL-12 decreased. During differentiation from MO to macrophages (MAC), interferon (IFN)-gamma-stimulated tumour cytotoxicity increased, but both MO and MAC were less cytotoxic upon rhuGM-CSF treatment. The differentiation-associated increase of LPS-induced TNF-alpha, IL-1RA and IL-10 secretion was reduced by the rhuGM-CSF treatment, and the expression of CD14 on MAC as well as the proportion of CD14+/CD16+, CD14+/MAX.1+ and CD14+/CD71+ cells in 7-d cultured MAC declined. We interpret these findings as (1) an increase of immature MO upon rhuGM-CSF therapy, (2) a priming effect on the LPS-induced proinflammatory cytokine repertoire of MO, and (3) an impact of rhuGM-CSF on the capacity of MO to differentiate to MAC in vitro.
Hennemann
B
B
Department of Haematology and Oncology, University of Regensburg, Germany.
Kreutz
M
M
Rehm
A
A
Andreesen
R
R
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D016130:Immunophenotyping; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008545:Melanoma / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D019798:Neopterin / Q000378:metabolism
D016207:Cytokines; D019798:Neopterin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor