雷洛昔芬在体内外研究中对刺激全血中细胞因子产生的影响。

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

作者信息

Kasai Yuka, Maegawa Masahiko, Yamamoto Satoshi, Kamada Masaharu, Yasui Toshiyuki, Uemura Hirokazu, Kobayashi Ayako, Kaneyama Masayo, Tani Anna, Matsui Sumika, Kuwahara Akira, Matsuzaki Toshiya, Furumoto Hiroyuki, Irahara Minoru

机构信息

Department of Obstetrics and Gynecology, Tokushima Prefectural Central Hospital, Tokushima, Japan.

出版信息

J Med Invest. 2011 Feb;58(1-2):110-7. doi: 10.2152/jmi.58.110.

DOI:10.2152/jmi.58.110

PMID:21372495

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.

摘要

目的

本研究旨在确定雷洛昔芬治疗对细胞因子产生的影响，以及雷洛昔芬对全血培养物中细胞因子产生的体外作用。

方法

我们获取了6名绝经后骨质疏松症女性在基线时、接受雷洛昔芬治疗3个月和6个月后的外周血样本，以及10名未接受雷洛昔芬治疗的绝经后女性的外周血样本。用脂多糖（LPS）或植物血凝素（PHA）刺激接受雷洛昔芬治疗女性的全血。将未接受雷洛昔芬治疗的绝经后女性的全血与浓度为10⁻¹⁰ - 10⁻⁷ M的雷洛昔芬预孵育，然后用LPS或PHA刺激。通过各自的酶联免疫吸附测定法（ELISA）测量上清液中白细胞介素-1β（IL-1β）、白细胞介素-4（IL-4）、白细胞介素-6（IL-6）、白细胞介素-12p40、白细胞介素-12p70、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）的浓度。

结果

在体外培养中，雷洛昔芬治疗抑制了LPS刺激的IL-1β、IL-6、IL-12p40、IL-12p70和TNF-α的产生，但不抑制PHA刺激的IL-4和IFN-γ的产生。在体外培养中，浓度为10⁻⁹ M的雷洛昔芬抑制了LPS刺激的IL-1β、IL-6和IL-12p40的产生以及PHA刺激的IFN-γ的产生。