G. Passeri et al., INCREASED INTERLEUKIN-6 PRODUCTION BY MURINE BONE-MARROW AND BONE-CELLS AFTER ESTROGEN WITHDRAWAL, Endocrinology, 133(2), 1993, pp. 822-828
We have previously shown that cytokine-induced production of interleuk
in-6 (IL-6) by cultured bone marrow-derived stromal and osteoblastic c
ells is inhibited by 17beta-estradiol, and that estrogen withdrawal (
ovariectomy) in mice causes an up-regulation of osteoclast development
which can be prevented by a neutralizing antibody against IL-6 or est
rogen replacement. To directly establish the link between estrogen los
s and altered IL-6 production, implied by our earlier studies, we have
now compared IL-6 production in ex vivo cultures of bone marrow cells
from mice that were sham operated, ovariectomized, or ovariectomized
and treated with 17beta-estradiol. In addition, we have examined the e
ffect of the in vitro withdrawal of estrogens from primary cell cultur
es of neonatal murine calvaria on IL-6 production. IL-6 production in
ex vivo cultures of bone marrow cells maintained in the presence of 1,
25-dihydroxyvitamin D3 or PTH was greater in marrow cells from ovariec
tomized mice than in those from sham-operated animals or ovariectomize
d animals receiving estrogen replacement. In line with this finding, a
ddition of 17beta-estradiol to calvaria cell cultures followed by with
drawal of the steroid caused an increase in the amount of IL-6 produce
d in response to the subsequent stimulation of these cultures with IL-
1 or PTH compared to that in cultures that had never been treated with
estradiol; when the inactive isomer 17alpha-estradiol was used, no ch
ange in IL-6 production was observed. These results establish that est
rogen loss causes an up-regulation of IL-6 production by bone marrow c
ells and that a similar phenomenon can be elicited in vitro by withdra
wal of 17beta-estradiol from primary cultures of bone cells.