ESTROGEN INHIBITS INTERLEUKIN-1-BETA-INDUCED INTERLEUKIN-6 PRODUCTIONBY HUMAN OSTEOBLAST-LIKE CELLS

Estrogen supplements are the primary pharmacologic intervention therap y to prevent and treat loss of bone mass (osteoporosis) in postmenopau sal women. Furthermore, at sites of local inflammation near bone, estr ogen-deficient women are significantly more susceptible to bone loss t han are estrogen-sufficient women. In the present study, we investigat e whether estrogen modulates osteoblast (MG-63) production of interleu kin-6 (IL-6), an osteoclast recruitment and differentiation of cytokin e, in the presence of the proinflammatory cytokine, IL-1 beta. Using e nzyme-linked immunosorbent assay (ELISA), we demonstrate that IL-1 bet a significantly enhances IL-6 secretion into culture supernatants in a dose-dependent and time-dependent manner. Using reverse-transcriptase polymerase chain reaction (RT-PCR) and ELISA respectively, we demonst rate further that levels of 17 beta-estradiol (active metabolite of es trogen) greater than or equal to those found in serum of estrogen-suff icient women inhibit steady-state IL-6 mRNA levels as well as inhibit secretion of IL-6 into culture supernatants. One mechanism by which es trogen therapy preserves bone mass in areas of inflammation may be via inhibition of IL-1 beta-stimulated obsteoblast-derived IL-6.