THE EFFECTS OF TENIDAP ON CYTOKINE-INDUCED PROLIFERATION OF HUMAN SYNOVIAL FIBROBLASTS IN-VITRO

Citation
Dl. Mattey et al., THE EFFECTS OF TENIDAP ON CYTOKINE-INDUCED PROLIFERATION OF HUMAN SYNOVIAL FIBROBLASTS IN-VITRO, Annals of the Rheumatic Diseases, 53(4), 1994, pp. 250-255
Citations number
30
Categorie Soggetti
Rheumatology
ISSN journal
00034967
Volume
53
Issue
4
Year of publication
1994
Pages
250 - 255
Database
ISI
SICI code
0003-4967(1994)53:4<250:TEOTOC>2.0.ZU;2-D
Abstract
Objectives-Tenidap, a new antirheumatic agent, is a Lipoxygenase and c yclooxygenase inhibitor, and is reported to inhibit the production and action of interleukin 1 (IL-1). Since eicosanoids, IL-1, and other cy tokines may influence the growth of fibroblasts in the joint synovium the study was carried out to determine the effects of Tenidap on cytok ine induced proliferation of these cells in vitro. Methods-Cell cultur es derived from patients with a variety of rheumatic diseases were cul tured in different concentrations of Tenidap sodium, with or without I L-1, tumour necrosis factor alpha (TNF), IL-6, basis fibroblast growth factor (bFGF), or transforming growth factor beta (TGF beta). Cell pr oliferation was measured using a crystal violent colourimetric assay. Prostaglandin E(2) levels in culture supernatants were measured by rad ioimmunoassay. Results-Tenidap at concentrations above 10 mu g/ml inhi bited cell growth, while at 1.25-5 mu g/ml there was a small but signi ficant increase in proliferation compared with controls. A further inc rease in growth was obtained when cells were incubated with Tenidap IL-1 induced growth by Tenidap was reduced by addition of high levels of exogenous PGE(2) (100 ng/ml) although growth was still higher than in IL-1 alone. Conclusions-Depending on concentration, Tenidap may inh ibit or stimulate synovial fibroblast growth. Our results suggest that augmentation of growth by low concentrations cannot be explained by i nhibition of PGE(2) production alone. Tenidap may directly stimulate c ell growth or may block other fibroblast factors which are involved in control of cytokine induced proliferation.