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

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Purpose : The aims of this study were to determine the effects of raloxifenetherapy on production of cytokines and in vitro effects of raloxifene on production ofcytokines by whole blood cultures. Methods :We obtained samples of peripheral bloodfrom 6 postmenopausal women with osteopenia at baseline and after 3 and 6 months ofraloxifene 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 whowere not treated with raloxifene was preincubated with raloxifene at concentrationsof 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 respectiveELISAs. Results : In ex vivo cultures, raloxifene therapy inhibited LPS-stimulated productionof IL-1β, IL-6, IL-12p40, IL-12p70 and TNF-α, but not PHA-stimulated productionof IL-4 and IFN-γ. In in vitro cultures, raloxifene at a concentration (10-9 M) inhibitedLPS-stimulated production of IL-1β, IL-6 and IL-12p40 and PHA-stimulated productionof 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 ofcytokines could play a role in the mechanisms of the osteoprotective effect of raloxifene.