Cytokine regulation of colony-stimulating factor production in cultured human synovial fibroblasts: I. Induction of GM-CSF and G-CSF production by interleukin-1 and tumor necrosis factor

Abstract

The cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF), induce a dose-dependent production of both granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte CSF (G-CSF) in cultured human synovial cells, as measured by immunoassay. With IL-1, significant levels of both CSFs were first detected within 6 to 12 hours, with a maximum reached 24 to 48 hours after commencement of stimulation. A synergistic effect was detected between IL-1 and TNF in production of both CSFs in these cells. No evidence was obtained for the IL-1-induced effect to be mediated by induction of endogenous TNF nor for the TNF-induced stimulation to involve IL-1. IL-1-stimulated synovial cells were shown to secrete biologically active GM-CSF and G- CSF, which were specifically inhibited by their respective monoclonal antibodies. The transcription inhibitor, actinomycin D, and protein synthesis inhibitor, cycloheximide, inhibited the increase in GM-CSF and G-CSF production induced by IL-1 and TNF. Finally, other cytokines, IL-3, interferon gamma (IFN gamma), IL-2, platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha), failed to stimulate either GM-CSF or G-CSF production, whether alone or in the presence of IL-1. These results suggest that cytokine-stimulated synovial fibroblasts may be a major source of intraarticular CSF production in the joints of patients with inflammatory arthritis; as a result, monocyte/macrophages and granulocytes may be activated, leading to perpetuation of the inflammation and destructive events occurring in these lesions.

Granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and granulocyte colony‐stimulating factor (G‐CSF) secretion by adherent monocytes measured by quantitative immunoassays

“…In other cell systems, IL-1 and T N F have synergistic effects on GM-CSF production (21)(22)(23). However, we did not find any evidence for either synergistic or additive effects of IL-1 and T N F on GM-CSF secretion by monocytes.…”

“…Immunoassays are both specific and quantitative and, therefore, are preferable as tools for measuring secretion of cytokines from defined cell populations. Only a limited number of reports have been published where immunoassays have been utilized for quantification of CSF secretion by fibroblasts (2 I), chondrocytes (22), human synovial cells (23), marrow stromal cells (16), T lymphocytes (24,25) and monocytes (26). The adherent cells studied in this report were 92-99% pure monocytes as estimated by unspecific esterase staining.…”

Serum interleukin‐6 level is a useful marker in evaluating therapeutic effects of levamisole and Chinese medicinal herbs on patients with oral lichen planus

“…High serum TNF-a level has been detected in about one third of OLP patients (14,24). Fibroblasts and endothelial cells can also be directly or indirectly responsible for IL-6 generation (25,26).…”

GM-CSF, IL-1α, IL-β, IL-6, IL-8, IL-10, ICAM-1 and VCAM-1 gene expression and cytokine production in human duodenal fibroblasts stimulated with lipopolysaccharide, IL-1α and TNF-α

“…Skin, synovial and pulmonary fibroblasts produce granulocyte-macrophage colony-stimulating faetor (GM-CSF). granulocyte colony-stimulating factor (G-CSF), leukaemia inhibitory factor (LiF), IL-1, IL-6 and IL-8 when stimulated with IL-1 or tumour necrosis factor (TNF) [1][2][3][4][5]. Adhesion molecules such as intercellular adhesion molecule-I (ICAM-I) and vascular cell adhesion moiecule-1 (VCAM-1) are expressed on the surface of fibroblasts [6,7], Cytokine secretion is increased by bacterial lipopolysaccharide (LPS) and viruses [8,9], suggesting a role in host defence.…”