Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

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

Abstract

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.