CHARACTERISTICS OF HUMAN SYNOVIAL FIBROBLAST ACTIVATION BY IL-1-BETA AND TNF-ALPHA

  • 1 February 1989
    • journal article
    • research article
    • Vol. 66  (2) , 196-200
Abstract
Human synovial fibroblast cell lines (HSN), established from tissues obtained from the knee joints of arthritis patients undergoing arthoplasty, were used to investigate the effects of human interleukin-1 (IL-1) .beta. and tumour necrosis factor (TNF).alpha. on proliferation and prostaglandin E2 (PGE2) secretion. IL-1.beta. and TNF.alpha. were equipotent stimulators of HSN proliferation. Classical non-steroidal anti-inflammatory drugs and glucocorticoids significantly augmented this effect. In addition, IL-1.beta. and TNF.alpha. were potent inducers of PGE2 production while exogenous PGE2 was growth inhibiting. These data suggest that the secretion of PGE2 by monokine-stimulated HSN exerts a negative feedback signal. Further examination of IL-1.beta.- and TNF.alpha.-induced PGE2 secretion revealed IL-1.beta. to be a more potent stimulator; however, this observation may be due, in part, to differences in the kinetics of induction. Rabbit anti-IL-1.beta. and anti-TNF.alpha. specifically neutralized both proliferation and PGE2 production induced by these monokines, but anti-IL-1.beta. (or anti-IL-1.alpha.) did not block TNF.alpha. activity. It is unclear whether TNF.alpha. stimulates HSN to produce IL-1, but the antibody data suggest that extracellular IL-1 is not responsible for TNF.alpha. in vitro activity.

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