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

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  • Kasai Yuka
    Department of Obstetrics and Gynecology, Tokushima Prefectural Central Hospital
  • Maegawa Masahiko
    Department of Obstetrics and Gynecology, Tokushima Prefectural Central Hospital
  • Yamamoto Satoshi
    Department of Obstetrics and Gynecology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Kamada Masaharu
    Department of Obstetrics and Gynecology, Health Insurance Naruto Hospital
  • Yasui Toshiyuki
    Department of Obstetrics and Gynecology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Uemura Hirokazu
    Department of Obstetrics and Gynecology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Kobayashi Ayako
    Department of Obstetrics and Gynecology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Kaneyama Masayo
    Department of Obstetrics and Gynecology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Tani Anna
    Department of Obstetrics and Gynecology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Matsui Sumika
    Department of Obstetrics and Gynecology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Kuwahara Akira
    Department of Obstetrics and Gynecology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Matsuzaki Toshiya
    Department of Obstetrics and Gynecology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Furumoto Hiroyuki
    Department of Obstetrics and Gynecology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Irahara Minoru
    Department of Obstetrics and Gynecology, Institute of Health Biosciences, the University of Tokushima Graduate School

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Abstract

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. J. Med. Invest. 58: 110-117, February, 2011

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