INFLAMMATORY CYTOKINES REGULATE PROLIFERATION OF CULTURED HUMAN OSTEOBLASTS

We investigated the effects of various pro-inflammatory cytokines on t he proliferation rate of isolated human osteoblastic cells in primary cultures. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-bet a (TNF-beta) time- and dose-dependently enhanced the proliferation of human osteoblasts. Both of these cytokines also enhanced endogenous pr ostaglandin E-2 (PGE(2)) formation. Exogenous PGE(2) dose- and time-de pendently-stimulated cell proliferation. However, the stimulatory effe cts of IL-1 beta and TNF-beta on osteoblast proliferation were not abo lished by indomethacin, indicating a direct effect by these cytokines on the rate of proliferation, TNF-alpha stimulated proliferation at lo w doses, while it significantly inhibited proliferation at higher conc entrations (at and above 100 pM) and with prolonged incubation times. This biphasic effect was unaffected by indomethacin. Interleukin-6, fi nally, did not affect the rate of proliferation. Our findings show tha t inflammatory cytokines may stimulate or inhibit the proliferation of isolated human osteoblasts, depending on concentration and time.