Recombinant human lymphotoxin effects on osteoblastic cells

Lymphotoxin, or tumor necrosis factor β, has been shown to be a potent bone resorbing cytokine. In the present study, the effect of recombinant human lymphotoxin on osteoblastic cell proliferation and prostaglandin synthesis was investigated. Lymphotoxin (10^-10-10^-7 M) caused a significant, dose-dependent decrease of rat osteoblastic cell proliferation. This appeared to be an indirect, prostaglandin-dependent action, since in the presence of indomethacin (1 μM) the lymphotoxin effect was reversed. Subsequently, prostaglandin E₂ and prostacyclin (assayed as 6-keto-prostaglandin F_1α levels produced by the osteoblastic cells in response to lymphotoxin were measured. The cytokine caused a dose-dependent increase of these arachidonic acid metabolites, with the maximum effect at 10^-8M. These results suggest that lymphotoxin's mechanism of action on bone may involve increases in arachidonic acid metabolite synthesis and an indirect, prostanoid-mediated decrease in the proliferation rate of osteoblastic cells.