Department of Medicine , Royal Melbourne Hospital , University of Melbourne , Parkville , Victoria , Australia .
Blood 76 : 1989-96 ( 1990)
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 .