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
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.