Interleukin-6 (IL-6), IL-1, receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin production by human osteoblastic cells: comparison of the effects of 17-beta oestradiol and raloxifene

Oestrogen inhibits bone resorption, at least in part, by regulating the production of several cytokines, including interleukin-6 (IL-6), IL-1, receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) by cells of the osteoblastic lineage. The selective oestrogen receptor modulator raloxifene (RAL) acts on bone in a similar manner to oestrogen, although the mechanisms of action of RAL on osteoblasts still remain unclear. We investigated and compared the effects of 17-beta oestradiol (E-2) and RAL on the regulation of IL-6, IL-1, RANKL and OPG in vitro in primary human osteoblastic (HOB) cells and in an immortalised clonal human bone marrow stromal cell line (HCC1) with osteoblastic characteristics. We tested E-2 and RAL at concentrations ranging from 10(-1)2 to 10(-6) M. IL-6, IL-1alpha and IL-1beta, OPG and RANKL were measured by ELISA. RANKL and OPG mRNA steady state level was assessed by quantitative PCR analysis. Both E-2 and RAL led to a significant reduction in IL-6 production in the HOB cells, although the effect was more marked with E-2 (P6 M) - HOB: 81.5 +/- 5-5*, 62.7 +/- 7.4*, 55.2 +/- 10.9*; HCC1: 92.7 +/- 7.4, 67 +/- 12.2*, 39 +/- 4.5*; *P