Interleukin-6 (IL-6) is a multifunctional cytokine whose circulating l
evels are under physiological conditions below detection, but whose pr
oduction is rapidly and strongly induced by several pathological and i
nflammatory stimuli. IL-6 has been implicated in a number of cell func
tions connected to immunity and hematopoiesis. Recently, it has been p
roposed to act as a stimulator of osteoclast formation and activity, i
n particular following estrogen depletion. The purpose of this study w
as to gain additional insights into the role of IL-6 during developmen
t, as well as in physiological and pathological conditions. We report
here that IL-6 deficient mice generated by gene targeting are viable a
nd do not present any evident phenotypic abnormality. However, analysi
s of bone metabolism revealed a specific bone phenotype. IL-6 deficien
t female mice have a normal amount of trabecular bone, but higher rate
s of bone turnover than control littermates. Estrogen deficiency induc
ed by ovariectomy causes in wild type animals a significant loss of bo
ne mass together with an increase in bone turnover rates. Strikingly,
ovariectomy does not induce any change in either bone mass or bone rem
odeling rates in the IL-6 deficient mice. These findings indicate that
IL-6 plays an important role in the local regulation of bone turnover
and, at least in mice, appears to be essential for the bone loss caus
ed by estrogen deficiency.