INFLUENCE OF HUMAN RECOMBINANT INTERLEUKIN-1-BETA ON HUMAN ARTICULAR-CARTILAGE - MITOTIC-ACTIVITY AND PROTEOGLYCAN METABOLISM

The effects of human recombinant interleukin-1-beta (IL-1-beta) were investigated on recently isolated (1 to 3 weeks) and on well-established (older than 3 weeks) monolayer cultured human articular chondrocytes. IL-1-beta was found to depress S-35-proteoglycan synthesis rates and to enhance prostaglandin E2 (PGE2) production in these monolayer cultured chondrocytes. Induction of S-35-proteoglycan-degradative activity by these cells also occurred in IL-1-beta treated cultures. These "catabolin" -IL-1 activities were observed in recently isolated as well-established "old" cultures. IL-1-beta increase H-3-thymidine incorporation rates in the "old" cultures. However, in recently isolated chondrocytes a dose-dependent reduction of the H-3-thymidine incorporation occurred. The depression of mitotic activity in these cells was partially abolished by indomethacin, indicating that this depression was a PGE2 effect. However, supplementing IL-1-beta with indomethacin did not raise the H-3-thymidine incorporation rates above the control levels. It can be concluded that IL-1-beta in itself is unable to induce proliferation in recently isolated cartilage cells. Our results suggest the possible existence of two different receptors for the different IL-1-beta activities. Hence, human articular chondrocytes respond differently to in vitro IL-1-beta exposure at different stages of differentiation.