Effects of raloxifene on the production of cytokines in stimulated whole blood in ex vivo and in vitro studies

Purpose : The aims of this study were to determine the effects of raloxifene
therapy on production of cytokines and in vitro effects of raloxifene on production of
cytokines by whole blood cultures. Methods :We obtained samples of peripheral blood
from 6 postmenopausal women with osteopenia at baseline and after 3 and 6 months of
raloxifene therapy and 10 postmenopausal women who did not receive raloxifene therapy.
Whole blood from raloxifene-treated women was stimulated with lipopolysaccharide
(LPS) or phytohemeagglutinin (PHA). Whole blood from postmenopausal women who
were not treated with raloxifene was preincubated with raloxifene at concentrations
of 10-10-10-7 M and then stimulated with LPS or PHA. Concentrations of IL-1β, IL-4, IL-6,
IL-12p40, IL-12p70, TNF-α and IFN-γ in the supernatant were measured by respective
ELISAs. Results : In ex vivo cultures, raloxifene therapy inhibited LPS-stimulated production
of IL-1β, IL-6, IL-12p40, IL-12p70 and TNF-α, but not PHA-stimulated production
of IL-4 and IFN-γ. In in vitro cultures, raloxifene at a concentration (10-9 M) inhibited
LPS-stimulated production of IL-1β, IL-6 and IL-12p40 and PHA-stimulated production
of IFN-γ. Conclusions : Raloxifene therapy decreases the production of IL-1β,
IL-6, IL-12 and TNF-α but not that of IL-4 and IFN-γ, suggesting that modulation of
cytokines could play a role in the mechanisms of the osteoprotective effect of raloxifene.

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