Recombinant human granulocyte/macrophage colony-stimulating factor enhances monocyte cytotoxicity and secretion of tumor necrosis factor alpha and interferon in cancer patients

Abstract

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.

Cytokines, GM-CSF and IFNγ administered by priming and post-chemotherapy cycling in recurrent ovarian cancer patients receiving carboplatin

“…In contrast, the mean fluorescent intensity (MFI) of CD32+ cells, which made up 100% of MOs before treatment with GM-CSF, increased significantly. Two previous studies had suggested that GM-CSF can stimulate antitumor functions, such as ADCC, or MO-mediated cytotoxicity[ 17 , 50 ] We found that after the administration of GM-CSF and rIFN-γ1b, there was an increase in the total number of MOs and activated subsets. However, there was no statistically significant enhancement of the MO-mediated cytotoxicity or ADCC effect after treatment.…”

TNF and Increased Intracellular Iron Alter Macrophage Polarization to a Detrimental M1 Phenotype in the Injured Spinal Cord

“…The 5 th -7 th highest upregulated cytokines are IFN-g (274-fold), TNF (252-fold), and lymphotoxin-a (LTa) (265-fold). Other cytokines of note include GM-CSF (36-fold increase), which is involved in increasing macrophage numbers in response to inflammation and, importantly, primes macrophages to respond to LPS challenge by increasing expression of TNF and IFN-g (Hamilton, 2002;Wing et al, 1989); IL-18 (13-fold increase), which also induces expression of IFN-g; and MIF (4-fold increase), which can suppress anti-inflammatory effects of glucocorticoids (Flaster et al, 2007) and could therefore suppress M2 polarization. Only six cytokines with anti-inflammatory properties were upregulated.…”

Use of rhu-GM-CSF in pulmonary tuberculosis patients: results of a randomized clinical trial

“…Human granulocyte-macrophage colonystimulating factor (hu-GM-CSF) is a cytokine, isolated by Nicola et al [17,18]. It has been used against neoplastic diseases to promote the enhancement of macrophage tumoricidal activity, in the treatment or prophylaxis of leukopenia associated with myelosuppressive therapies, and in patients with bone marrow failure [19,20]. Also, GM-CSF increases the number of leukocytes in the peripheral circulation and enhances granulocyte and monocyte function [21].…”