Effect of granulocyte‐macrophage colony‐stimulating factor treatment on phenotype, cytokine release and cytotoxicity of circulating blood monocytes and monocyte‐derived macrophages

• Published in: British journal of haematology 1998-09, Vol.102 (5), p.1197-1203
• Main Authors: HENNEMANN, B, KREUTZ, M, REHM, A, ANDREESEN, R
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Biological and medical sciences; Carcinoma, Renal Cell - immunology; Carcinoma, Renal Cell - pathology; Carcinoma, Renal Cell - therapy; Cell Differentiation; Cytokines - metabolism; cytotoxicity; Cytotoxicity, Immunologic; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use; granulocyte‐macrophage colony‐stimulating factor; Humans; Immunophenotyping; Immunotherapy; Kidney Neoplasms - immunology; Kidney Neoplasms - pathology; Kidney Neoplasms - therapy; Macrophages - immunology; Macrophages - pathology; Medical sciences; Melanoma - immunology; Melanoma - pathology; Middle Aged; monocytes; Monocytes - immunology; Monocytes - pathology; Neopterin - metabolism; Pharmacology. Drug treatments; phenotype
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.1998.00922.x

We studied phenotype, function and differentiation of mononuclear phagocytes in 11 cancer patients treated subcutaneously with 10 μg/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)‐α, 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‐α, IL‐6 and IL‐1RA increased initially, whereas IL‐1β, IL‐10 and IL‐12 decreased. During differentiation from MO to macrophages (MAC), interferon (IFN)‐γ‐stimulated tumour cytotoxicity increased, but both MO and MAC were less cytotoxic upon rhuGM‐CSF treatment. The differentiation‐associated increase of LPS‐induced TNF‐α, 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.