Search results for "Colony-Stimulating Factors"
showing 10 items of 14 documents
Hematologic effects of recombinant human granulocyte colony-stimulating factor in patients with malignancy.
1989
Abstract The effect of recombinant human granulocyte colony-stimulating factor (G-CSF) on hematologic parameters was evaluated in a phase I clinical study in 18 patients with advanced malignancy. G-CSF was administered once daily as a 30-minute infusion for 14 days; three patients each were treated at increasing dose levels of 1, 3, 10, 30, and 60 micrograms kg-1 day-1. A transient decrease in neutrophil and monocyte counts was observed immediately after the G-CSF infusion, followed by a dose-dependent increase of up to 15-fold. G-CSF-induced neutrophils exhibited an increased O2- radical production, and serum levels of enzymes related to granulocyte turnover, including lysozyme and elastas…
Hematopoietic responses in patients with advanced malignancy treated with recombinant human granulocyte-macrophage colony-stimulating factor.
1989
The in vivo effect of yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) was investigated in 30 patients with advanced malignancy in a phase Ib trial. Patients were treated at four different dose levels (120 to 1,000 micrograms/m2/d) by either daily intravenous (IV) bolus injection or 24-hour continuous infusion. Administration of rh GM-CSF resulted in a broad spectrum of dose- and schedule-dependent hematopoietic effects. Sustained infusion of rh GM-CSF elicited a maximum 17-fold average peak increase of the total WBC count with mainly neutrophils, eosinophils, and monocytes accounting for this rise, and increases in bone marrow cellularity with a…
Recombinant human granulocyte-macrophage colony-stimulating factor induces secretion of autoinhibitory monokines by U-937 cells
1988
Colony-stimulating factors are required for survival proliferation, differentiation and functional activation of granulocytes, macrophages and their precursor cells. In the present report, however, we demonstrate antiproliferative activity of recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) on monoblast cell line U-937 and provide evidence for the involvement of tumor necrosis factor alpha TNF-alpha and interleukin 1 beta (IL 1 beta) in its growth inhibitory action. GM-CSF (but not granulocyte CSF, G-CSF or macrophage CSF, M-CSF) suppressed DNA synthesis and self renewal of U-937 cells. Similarly, medium conditioned by U-937 cells in response to GM-CSF (GM-CS…
Role of colony‐stimulating factors in the biology of acute myelogenous leukemia
1989
A high proportion of acute myeloid leukemias (AML) recently investigated for their capacity to synthesize biologically active bioregulatory molecules was found to accumulate messenger (m) RNA and to produce membrane-bound or -secreted forms of stimulating factors for granulocyte, macrophage and mixed granulocyte-macrophage colony growth. Blast cells have also been found to secrete interleukin 1, tumor necrosis factor-alpha, interleukin 6, and to express receptors for various growth factors as well. However, growth factors like interleukin 2 and interleukin 3 have not been identified as AML products, and several other factors including interleukin 4, interleukin 5, etc. need further evaluati…
Modulation of Forssman Glycosphingolipid Expression by Murine Macrophages: Coinduction with Class II MHC Antigen by the Lymphokines IL4 and IL6
1990
In contrast to murine spleen M phi, resident peritoneal M phi from health mice express very little Forssman glycolipid antigen (Fo). The following experiments suggest that Fo expression by peritoneal M phi may be associated with inflammation. Balb/c and CBA/J mice were given inflammatory stimuli by i.p. injection of live BCG, thioglycollate (TG), Corynebacterium parvum (CP), proteose peptone (PP), or LPS. Control animals received pyrogen-free saline. Expression of Fo and Ia antigen by peritoneal M phi was determined by immunofluorescence after 4 d. Application of TG or CP led to an up to 30-fold increase in Fo+, Ia+ double positive M phi over that in control animals. LPS caused mainly an in…
Granulocyte-macrophage colony-stimulating factor induces cytokine secretion by human polymorphonuclear leukocytes.
1989
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known as an inducer of proliferation and functional activation of myeloid cells. This study was carried out to characterize the effects of GM-CSF on polymorphonuclear leukocytes (PMN) more extensively. Using Northern blot analysis, we show that PMN are able to accumulate mRNAs for different cytokines, including tumor necrosis factor-alpha (TNF-alpha); G-CSF, and M-CSF, all of which are involved in inflammation and hematopoiesis. Biological assays and immunoassays demonstrate that PMN translate these mRNAs, except TNF-alpha, into secretory proteins. However, the expression of these cytokines is dependent on stimulation by exogenous…
Production of macrophage-, granulocyte-, granulocyte-macrophage- and multi-colony-stimulating factor by peripheral blood cells
1989
The specific cell sources and signals for induction of various colony-stimulating factors (CSF) in peripheral blood mononuclear cells (PBMC), purified T lymphocyte and monocyte (Mo) populations have been investigated. In the absence of exogenous activating stimuli, human PBMC, T cells and Mo failed to produce stable cytoplasmic mRNA for CSF for macrophages (M-CSF or CSF-1), for granulocytes (G-CSF), for granulocytes and macrophages (GM-CSF) and for multilineage CSF [multi-CSF, interleukin (IL) 3] and thus failed to release CSF proteins. However, after stimulation with phorbol myristate acetate and phytohemagglutinin, M-, G-, GM- and multi-CSF mRNA became detectable in PBMC, resulting in the…
Tumor necrosis factor (TNF)-alpha but not TNF-beta induces secretion of colony stimulating factor for macrophages (CSF-1) by human monocytes
1987
Abstract Tumor necrosis factor (TNF)-alpha has been identified as a major inducer of colony stimulating factor (CSF)-secretion by human vascular endothelial cells and fibroblasts. In the present study we assessed the capacity of TNFs to induce release of CSF-1 from highly purified peripheral blood monocyte preparations. Whereas monocytes do not accumulate CSF-1 messenger (m)RNA constitutively and consequently do not produce CSF-1 protein, CSF-1 mRNA and protein secretion became detectable, when monocytes were cultured in the presence of TNF-alpha, that was synergistically enhanced by interferon-gamma (IFN-gamma). However, under identical experimental conditions TNF-beta failed to induce mon…
Effect of granulocyte-macrophage colony-stimulating factor on neutropenia and related morbidity induced by myelotoxic chemotherapy.
1990
Abstract purpose: A phase Ib/II clinical study was undertaken to assess the efficacy of recombinant human (rh) granulocyte-macrophage colony-stimulating (GM-CSF) factor in attenuating neutropenia and associated morbidity caused by high-dose anticancer chemotherapy administered in the presence or absence of autologous bone marrow support. patients and methods: Twenty-two patients with various solid tumors and lymphoid neoplasias were treated with a single daily subcutaneous dose of rh GM-CSF (250/μg/m 2 ) 48 hours after receiving a second cycle of highly myelotoxic chemotherapy for a period of 10 days. Within-subject comparisons on neutropenia-related clinical and laboratory variables were m…
Interleukin-4 induces secretion of CSF for granulocytes and CSF for macrophages by peripheral blood monocytes.
1989
Abstract T cells are known to interact cooperatively with monocytes to produce Colony-Stimulating Factors (CSF), although T cell-mediated signals leading to CSF secretion by monocytes are not completely understood. We have made use of Northern blot hybridization and specific bioassays to study the effects of the T cell product interleukin-4 (IL-4) on monocyte CSF expression. The results suggest a previously unrecognized role of IL-4 as a CSF inducer since exposure of monocytes to IL-4 resulted in accumulation of transcripts for granulocyte-CSF (G-CSF) and macrophage-CSF (M-CSF). Consequently, IL-4-activated monocytes released factors in their culture supernatants biologically and antigenica…