title: Characteristics of human synovial fibroblast activation by IL-1 beta and TNF alpha.
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.
authors: Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285.
authors: B D
authors: BD
authors: Gitter
authors: J M
authors: JM
authors: Labus
authors: S L
authors: SL
authors: Lees
authors: M E
authors: ME
authors: Scheetz
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D015232:Dinoprostone / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone