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Raloxifene reduces circulating levels of interleukin-7 and monocyte chemoattractant protein-1 in postmenopausal women

      Abstract

      Objective

      The aim of the present study was to determine the effects of raloxifene on changes in circulating levels of cytokines and chemokines in relation to changes in lipid profiles and markers of inflammation in postmenopausal women.

      Methods

      Fifty-three postmenopausal women aged 45–65 years old were randomly assigned in open, parallel-group fashion to a control group or raloxifene group. Twenty-six women received oral administration of 60 mg raloxifene every day and 27 women did not receive any drugs for 12 months. Serum cytokines levels were simultaneously measured using a multiplexed human cytokine assay.

      Results

      Serum IL-7 concentrations in women who received raloxifene were decreased significantly (p = 0.014), and serum monocyte chemoattractant protein (MCP)-1 concentrations in women who received raloxifene were decreased significantly (p = 0.0003) at 12 months. In the control group, serum levels of MCP-1 and IL-7 did not show significant changes. There were significant differences (p = 0.032 and p = 0.0024, respectively) in percentage changes in IL-7 and MCP-1 in the control group and in the raloxifene group. Levels of low-density lipoprotein cholesterol (LDL-C) and E-selectin were decreased significantly in women who received raloxifene, but the percentage changes in LDL-C and E-selectin over a period of 12 months were not significantly correlated with percentage changes in IL-7 and MCP-1 over the same period.

      Conclusion

      Circulating levels of IL-7 and MCP-1 decrease in postmenopausal women who received raloxifene.

      Keywords

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      References

        • Kern P.A.
        • Ranganathan S.
        • Li C.
        • Wood L.
        • Ranganathan G.
        Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance.
        Am J Physiol Endocrinol Metab. 2001; 280: E745-E751
        • Tedgui A.
        • Mallat Z.
        Cytokines in atherosclerosis: pathogenic and regulatory pathways.
        Physiol Rev. 2006; 86: 515-581
        • Lagathu C.
        • Yvan-Charvet L.
        • Bastard J.P.
        • et al.
        Long-term treatment with interleukin-1 beta induces insulin resistance in murine and human adipocytes.
        Diabetologia. 2006; 49: 2162-2173
        • Sartipy P.
        • Loskutoff D.J.
        Monocyte chemoattractant protein 1 in obesity and insulin resistance.
        Proc Natl Acad Sci USA. 2003; 100: 7265-7270
        • Kim C.S.
        • Park H.S.
        • Kawada T.
        • et al.
        Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters.
        Int J Obes. 2006; 30: 1347-1355
        • Reape T.J.
        • Groot P.H.
        Chemokines and atherosclerosis.
        Atherosclerosis. 1999; 147: 213-225
        • Maury E.
        • Ehala-Aleksejev K.
        • Guiot Y.
        • et al.
        Adipokines oversecreted by omental adipose tissue in human obesity.
        Am J Physiol Endocrinol Metab. 2007; 293: E656-E665
        • Barrett-Connor E.
        • et al.
        Raloxifene and cardiovascular events in osteoporotic postmenopausal women.
        JAMA. 2002; 287: 847-857
        • Takahashi K.
        • Mori-Abe A.
        • Takata K.
        • et al.
        Raloxifene improves the ovariectomy-induced impairment in endothelium-dependent vasodilation.
        Menopause. 2007; 14: 656-661
        • Colacurci N.
        • Manzella D.
        • Fornaro F.
        • Carbonella M.
        • Paolisso G.
        Endothelial function and menopause: effects of raloxifene administration.
        J Clin Endocrinol Metab. 2003; 88: 2135-2140
        • Griffiths K.A.
        • Sader M.A.
        • Skilton M.R.
        • Harmer J.A.
        • Celermajer D.S.
        Effects of raloxifene on endothelium-dependent dilation, lipoproteins, and markers of vascular function in postmenopausal women with coronary artery disease.
        J Am Coll Cardiol. 2003; 42: 698-704
        • Ceresini G.
        • Marchini L.
        • Rebecchi I.
        • et al.
        Effects of raloxifene on carotid blood flow resistance and endothelium-dependent vasodilation in postmenopausal women.
        Atherosclerosis. 2003; 167: 121-127
        • Barrett-Connor E.
        • et al.
        Effects of raloxifne on cardiovascular events and breast cancer in postmenopausal women.
        N Engl J Med. 2006; 355: 125-137
        • Colacurci N.
        • Fornaro F.
        • Cobellis L.
        • et al.
        Raloxifene slows down the progression of intima-media thickness in postmenopausal women.
        Menopause. 2007; 14: 879-884
        • Blum A.
        • Schenke W.H.
        • Hathaway L.
        • et al.
        Effects of estrogen and the selective estrogen receptor modulator raloxifene on markers of inflammation in postmenopausal women.
        Am J Cardiol. 2000; 86: 892-895
        • Walsh B.W.
        • Cox D.A.
        • Sashegyi A.
        • et al.
        Role of tumor necrosis factor-α and interleukin-6 in the effects of hormone replacement therapy and raloxifene on C-reactive protein in postmenopausal women.
        Am J Cardiol. 2001; 88: 825-828
        • Gianni W.
        • Ricci A.
        • Gazzaniga P.
        • et al.
        Raloxifene modulates interleukin-6 and tumor necrosis factor-α synthesis in vivo: results from a pilot clinical study.
        J Clin Endocrinol Metab. 2004; 89: 6097-6099
        • Yasui T.
        • Maegawa M.
        • Tomita J.
        • et al.
        Changes in serum cytokine concentrations during the menopausal transition.
        Maturitas. 2007; 56: 396-403
        • Ligthart G.J.
        • Corberand J.X.
        • Fournier C.
        • et al.
        Admission criteria for immunogerontological studies in man: the SENIEUR protocol.
        Mech Ageing Dev. 1984; 28: 47-55
        • Murase Y.
        • Kobayashi J.
        • Nohara A.
        • et al.
        Raloxifene promotes adipocyte differentiation of 3T3-L1 cells.
        Eur J Pharmacol. 2006; 538: 1-4
        • Dus D.
        • Krawczenko A.
        • Zalecki P.
        • et al.
        IL-7 receptor is present on human microvascular endothelial cells.
        Immunol Lett. 2003; 68: 163-168
        • Krishnaswamy G.
        • Kelley J.
        • Yerra L.
        • Smith J.K.
        • Chi D.S.
        Human endothelium as a source of multifunctional cytokines: molecular regulation and possible role in human disease.
        J Interferon Cytokine Res. 1999; 19: 91-104
        • Yla-Herttuala S.
        • Lipton B.A.
        • Rosenfeld M.E.
        • et al.
        Expression of monocyte chemoattractant protein 1 in macrophage-rich areas of human and rabbit atherosclerotic lesions.
        Proc Natl Acad Sci USA. 1991; 88: 5252-5256
        • Seli E.
        • Pehlivan T.
        • Selam B.
        • Garcia-Velasco J.A.
        • Arici A.
        Estradiol down-regulates MCP-1 expression in human coronary artery endothelial cells.
        Fertil Steril. 2002; 77: 542-547
        • Takahashi K.
        • Mizuarai S.
        • Araki H.
        • et al.
        Adiposity elevates plasma MCP-1 levels leading to the increased CD11b-positive monocytes in mice.
        J Biol Chem. 2003; 278: 46654-46660
        • Miyatani Y.
        • Yasui T.
        • Uemura H.
        • et al.
        Associations of circulating adiponectin with estradiol and monocyte chemotactic protein-1 in postmenopausal women.
        Menopause. 2008; 15: 536-541
        • Han K.H.
        • Tangirala R.K.
        • Green S.R.
        • Quehenberger O.
        Chemokine receptor CCR2 expression and monocyte chemoattractant protein-1-mediated chemotaxis in human monocytes. A regulatory role for plasma LDL.
        Arterioscler Thromb Vas Biol. 1998; 18: 1983-1991
        • Cushing S.D.
        • Berliner J.A.
        • Valente A.J.
        • et al.
        Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells.
        Proc Natl Acad Sci USA. 1990; 87: 5134-5138
        • Rezaie-Majd A.
        • Maca T.
        • Bucek R.A.
        • et al.
        Simvastatin reduces expression of cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 in circulating monocytes from hypercholesterolemic patients.
        Arterioscler Thromb Vasc Biol. 2002; 22: 1194-1199
        • Ozmen B.
        • Kirmaz C.
        • Aydin K.
        • et al.
        Influence of the selective oestrogen receptor modulator (raloxifne hydrochloride) on IL-6, TNF-α. TGF-β1 and bone turnover markers in the treatment of postmenopausal osteoporosis.
        Eur Cytokine Netw. 2007; 18: 148-153
        • Yasui T.
        • Maegawa M.
        • Tomita J.
        • et al.
        Association of serum cytokine concentrations with psychological symptoms in midlife women.
        J Reprod ImmunoI. 2007; 75: 56-62
        • Alesci S.
        • Martinez P.E.
        • Kelkar S.
        • et al.
        Major depression is associated with significant diurnal elevations in plasma interleukin-6 levels, a shift of its circadian rhythm, and loss of physiological complexity in its secretion: clinical implications.
        J Clin Endocrinol Metab. 2005; 90: 2522-2530
        • Judd A.M.
        • Call G.B.
        • Barney M.
        • et al.
        Possible function of IL-6 and TNF as intraadrenal factors in the regulation of adrenal steroid secretion.
        Ann N Y Acad Sci. 2000; 917: 628-637
        • Bruun J.M.
        • Lihn A.S.
        • Madan A.K.
        • et al.
        Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue.
        Am J Physiol Endocrinol Metab. 2004; 286: E8-E13
        • Yasui T.
        • Uemura H.
        • Tomita J.
        • et al.
        Association of interleukin-8 with hot flashes in premenopausal, perimenopausal, and postmenopausal women and bilateral oophorectomized women.
        J Clin Endocrinol Metab. 2006; 91: 4805-4808
        • Baek K.H.
        • Oh K.W.
        • Lee W.Y.
        • et al.
        Changes in the serum sex steroids. IL-7 and RANKL-OPG system after bone marrow transplantation: influences on bone and mineral metabolism.
        Bone. 2006; 39: 1352-1360
        • Weitzmann M.N.
        • Roggia C.
        • Toraldo G.
        • Weitzmann L.
        • Pacifici R.
        Increased production of IL-7 uncouples bone formation from bone resorption during estrogen deficiency.
        J Clin Invest. 2002; 110: 1643-1650
        • Cheung J.
        • Mak Y.T.
        • Papaioannuou S.
        • et al.
        Interleukin-6 (IL-6), IL-1, receptor activator of nuclear κB ligand (RANKL) and osteoprotegerin production by human osteoblastic cells: comparison of the effect of 17β-oestradiol and raloxifene.
        J Endocrinol. 2003; 177: 423-433