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

Abstract

Observational studies 1 Cushman M Meilahn E.N Psaty B.M Kuller L.H Dobs A.S Tracy R.P Hormone replacement therapy, inflammation, and hemostasis in elderly women. Arterioscler Thromb Vasc Biol. 1999; 19: 893-899 Crossref PubMed Scopus (220) Google Scholar , 2 Ridker P.M Hennekens C.H Rifai N Buring J.E Manson J.E Hormone replacement therapy and increased plasma concentration of C-reactive protein. Circulation. 1999; 100: 713-716 Crossref PubMed Scopus (424) Google Scholar and randomized trials 3 van Baal W.M Kenemans P van der Mooren M.J Kessel H Emeis J.J Stehouwer C.D Increased C-reactive protein levels during short-term hormone replacement therapy in healthy postmenopausal women. Thromb Haemost. 1999; 81: 925-928 PubMed Google Scholar , 4 Cushman M Legault C Barrett-Connor E Stefanick M.L Kessler C Judd H.L Sakkinen P.A Tracy R.P Effect of postmenopausal hormones on inflammation-sensitive proteins The postmenopausal Estrogen/Progestin interventions (PEPI) study. Circulation. 1999; 100: 717-722 Crossref PubMed Scopus (621) Google Scholar have demonstrated that estrogen therapy with and without concomitant progestin increases the serum level of C-reactive protein (CRP) in postmenopausal women. CRP, a circulating marker of inflammation, is an independent risk factor for cardiovascular events in healthy postmenopausal women. 5 Ridker P.M Hennekens C.H Buring J.E Rifai N C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 1999; 342: 836-843 Crossref Scopus (4967) Google Scholar The serum concentration of CRP correlates with that of tumor necrosis factor-α (TNF-α) 6 Ridker P.M Rifai N Pfeffer M Sacks F Lepage S Braunwald E Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation. 1999; 101: 2149-2153 Crossref Scopus (824) Google Scholar and interleukin-6 (IL-6), 7 Ridker P.M Rifai N Stampfer M.J Hennekens C.H Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 1999; 101: 1767-1772 Crossref Scopus (1986) Google Scholar the primary stimulant of hepatic CRP production. 8 Baumann H Gauldie J The acute phase response. Immunol Today. 1999; 15: 74-80 Abstract Full Text PDF Scopus (428) Google Scholar Raloxifene is a selective estrogen receptor modulator used clinically for the prevention and treatment of postmenopausal osteoporosis, 9 Kauffman R.F Bryant H.U Yang N Harper K Huster W.J Walls E Lufkin E.G Preventing postmenopausal osteoporosis An update on raloxifene. Drug News Perspect. 1999; 12: 223-233 Google Scholar and is also under investigation for its effect on the risk of major cardiovascular events in postmenopausal women. 10 Barrett-Connor E Wenger N.K Grady D Mosca L Collins P Kornitzer M Cox D.A Moscarelli E Anderson P.W Hormone and nonhormone therapy for the maintenance of postmenopausal health The need for randomized controlled trials of estrogen and raloxifene. J Women’s Health. 1999; 7: 839-847 Crossref Scopus (70) Google Scholar Unlike estrogen, raloxifene does not increase CRP levels in postmenopausal women, 11 Walsh B.W Paul S Wild R.A Dean R.A Tracy R.P Cox D.A Anderson P.W The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women A randomized, controlled trial. J Endocrinol Metabol. 1999; 85: 214-218 Google Scholar , 12 Blum A Schenke W.H Hathaway L Mincemoyer R Csako G Waclawiw M.A Cannon R.O Effects of estrogen and the selective estrogen receptor modulator raloxifene on markers of inflammation in postmenopausal women. Am J Cardiol. 1999; 86: 892-895 Abstract Full Text Full Text PDF Scopus (37) Google Scholar although the mechanism for this difference remains unclear. We hypothesized that the differing effects of hormone replacement therapy (HRT) and raloxifene on serum CRP concentrations may be due to different effects on selected proinflammatory cytokines, such as IL-6 and TNF-α. This study compared the effects of HRT and raloxifene on the serum concentrations of TNF-α and IL-6, and assessed the relation between these effects and changes in serum CRP observed in the same population of postmenopausal women.