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 phag ocytes in 11 cancer patients treated subcutaneously with 10 mu g/kg re combinant 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 d ecrease of CD14(bright)/CD16(bright) cells with a diminution of the me an fluorescence intensity (MFI) of CD14, and (3) a decrease of MO cell ular cytotoxicity. In patients' sera, tumour necrosis factor (TNF)-alp ha, interleukin (IL)-10, IL-12, neopterin, macrophage-colony-stimulati ng factor (M-CSF), and IL-1 receptor antagonist (IL-1RA) increased, wh ereas GM-CSF and granulocyte-colony-stimulating factor (G-CSF) decreas ed after an initial peak. In whole blood samples the lipopolysaccharid e (LPS)-stimulated release of TNF-alpha, IL-6 and IL-1RA increased ini tially, whereas IL-1 beta, IL-10 and IL-12 decreased. During different iation from MO to macrophages (MAC), interferon (IFN)-gamma-stimulated tumour cytotoxicity increased, but both MO and MAC were less cytotoxi c 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(+) ce lls in 7-d cultured MAC declined. We interpret these findings as (1) a n 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.