Human recombinant interleukin‐1β stimulates glycosaminoglycan production in human synovial fibroblast cultures

AbstractHuman recombinant interleukin‐1β (rIL‐1β) stimulated glycosaminoglycan (GAG) production in human synovial fibroblast cultures. A dose‐dependent increase in GAG production was found, to a maximum of 500%. Increase was detected at doses as low as 1 pg/ml of rIL‐1β, reached a maximum at 10‐100 pg/ml, and was apparent 10 hours after addition of rIL‐1β. Stimulation of GAG was always accompanied by increased accumulation of prostaglandin E (PGE) in culture media and by increased collagenase production in approximately one‐half the experiments. Indomethacin (5 m̈/ml) completely inhibited PGE stimulation by rIL‐1β, but only partially inhibited that of GAG overproduction and had no effect on collagenase production. Hydrocortisone (2 m̈/ml) inhibited stimulation of all 3 parameters. Stimulation of hyaluronate in synovial cultures prevailed over that of sulfated GAG, which occurred to à lesser extent. Our results support earlier suggestions that interleukin‐1 is a major active mononuclear cell factor that is capable of inducing profound changes in connective tissue cell function.