Etidronate inhibits the production of IL-6 by osteoblast-like cells

IL-6 is a resorbing cytokine synthesized by osteoblasts and monocytes that has been implicated in the pathogenesis of osteoporosis. Bisphosphonates are well-known antiresorptive drugs, the antiosteoclastic effect of which has been recently suggested to be brought about at least in part through osteoblasts. Based on these facts, we have studied the effect of etidronate on the production of IL-6 by two tumoral cell lines of human osteoblastic phenotype (MG63 and SaOs cells), and by peripheral blood mononuclear cells (PBMC). For comparison, another antiresorptive drug, estradiol, was included in the study. MG63 cells were stimulated with LPS and IL-1 beta, SaOs cells with LPS, IL-1 beta and PMA, and PBMC with LPS and PMA. Etidronate was tested at 10(-7), 10(-6), 10(-5), and 10(-4) M, and 17beta-estradiol was tested at 10(-10), 10(-9), 10(-8), and 10(-7) M. IL-6 was determined in supernatants by an ELISA. No significant effect of either etidronate or estradiol on IL-6 secretion by LPS or PMA-stimulated PBMC was found. However, in osteoblastic-like cells, an inhibition of IL-6 production by etidronate in LPS-stimulated cultures was found. At the highest concentrations tested, IL-6 production values were 58 +/- 9% and 53 +/- 8% of those at base line for MG63 and SaOs cells, respectively. Estradiol did not modify IL-6 secretion under any condition. In conclusion, our study supports the contention that the antiresorptive effect of bisphosphonates may be due in part to a decrease in IL-6 production by osteoblasts.