This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pfeilschifter, J. Articles by Schatz, H. Search for Related Content PubMed PubMed Citation Articles by Pfeilschifter, J. Articles by Schatz, H.

Changes in Proinflammatory Cytokine Activity after Menopause

Department of Internal Medicine, Berufsgenossenschaftliche Kliniken Bergmannsheil, University of Bochum, D-44789 Bochum, Germany

Correspondence: Address all correspondence and requests for reprints to: Johannes Pfeilschifter, M.D., Berufsgenossenschaftliche Kliniken Bergmannsheil, University of Bochum, Department of Internal Medicine, Bürkle-de-la-Camp-Platz 1, D-44789 Bochum, Germany. E-mail: Johannes.Pfeilschifter{at}ruhr-uni-bochum.de

There is now a large body of evidence suggesting that the decline in ovarian function with menopause is associated with spontaneous increases in proinflammatory cytokines. The cytokines that have obtained the most attention are IL-1, IL-6, and TNF-. The exact mechanisms by which estrogen interferes with cytokine activity are still incompletely known but may potentially include interactions of the ER with other transcription factors, modulation of nitric oxide activity, antioxidative effects, plasma membrane actions, and changes in immune cell function. Experimental and clinical studies strongly support a link between the increased state of proinflammatory cytokine activity and postmenopausal bone loss. Preliminary evidence suggests that these changes also might be relevant to vascular homeostasis and the development of atherosclerosis. Better knowledge of the mechanisms and the time course of these interactions may open new avenues for the prevention and treatment of some of the most prevalent and important disorders in postmenopausal women.

This article has been cited by other articles:

				K. O. Badellino, M. L. Wolfe, M. P. Reilly, and D. J. Rader Endothelial Lipase Is Increased In Vivo by Inflammation in Humans Circulation, February 5, 2008; 117(5): 678 - 685. [Abstract] [Full Text] [PDF]

				L. Shu, S.-M. Guan, S.-M. Fu, T. Guo, M. Cao, and Y. Ding Estrogen Modulates Cytokine Expression in Human Periodontal Ligament Cells J. Dent. Res., February 1, 2008; 87(2): 142 - 147. [Abstract] [Full Text] [PDF]

				L. Shu, S.-M. Guan, S.-M. Fu, T. Guo, M. Cao, and Y. Ding Estrogen Modulates Cytokine Expression in Human Periodontal Ligament Cells Journal of Dental Research, February 1, 2008; 87(2): 142 - 147. [Abstract] [Full Text] [PDF]

				A. Cvoro, D. Tatomer, M.-K. Tee, T. Zogovic, H. A. Harris, and D. C. Leitman Selective Estrogen Receptor- Agonists Repress Transcription of Proinflammatory Genes J. Immunol., January 1, 2008; 180(1): 630 - 636. [Abstract] [Full Text] [PDF]

				N. D Freedman, W.-H. Chow, Y.-T. Gao, X.-O. Shu, B.-T. Ji, G. Yang, J. H Lubin, H.-L. Li, N. Rothman, W. Zheng, et al. Menstrual and reproductive factors and gastric cancer risk in a large prospective study of women Gut, December 1, 2007; 56(12): 1671 - 1677. [Abstract] [Full Text] [PDF]

				F. Eskandari, P. E. Martinez, S. Torvik, T. M. Phillips, E. M. Sternberg, S. Mistry, D. Ronsaville, R. Wesley, C. Toomey, N. G. Sebring, et al. Low Bone Mass in Premenopausal Women With Depression Arch Intern Med, November 26, 2007; 167(21): 2329 - 2336. [Abstract] [Full Text] [PDF]

				D. Fuchs, K. Vafeiadou, W. L Hall, H. Daniel, C. M Williams, J. H Schroot, and U. Wenzel Proteomic biomarkers of peripheral blood mononuclear cells obtained from postmenopausal women undergoing an intervention with soy isoflavones Am. J. Clinical Nutrition, November 1, 2007; 86(5): 1369 - 1375. [Abstract] [Full Text] [PDF]

				A. K. Sasser, N. J. Sullivan, A. W. Studebaker, L. F. Hendey, A. E. Axel, and B. M. Hall Interleukin-6 is a potent growth factor for ER-{alpha}-positive human breast cancer FASEB J, November 1, 2007; 21(13): 3763 - 3770. [Abstract] [Full Text] [PDF]

				F. Grassi, G. Tell, M. Robbie-Ryan, Y. Gao, M. Terauchi, X. Yang, M. Romanello, D. P. Jones, M. N. Weitzmann, and R. Pacifici Oxidative stress causes bone loss in estrogen-deficient mice through enhanced bone marrow dendritic cell activation PNAS, September 18, 2007; 104(38): 15087 - 15092. [Abstract] [Full Text] [PDF]

				R. H. Straub The Complex Role of Estrogens in Inflammation Endocr. Rev., August 1, 2007; 28(5): 521 - 574. [Abstract] [Full Text] [PDF]

				J. L. Turgeon, M. C. Carr, P. M. Maki, M. E. Mendelsohn, and P. M. Wise Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies Endocr. Rev., October 1, 2006; 27(6): 575 - 605. [Abstract] [Full Text] [PDF]

				J. L. Downs and H. F. Urbanski Neuroendocrine Changes in the Aging Reproductive Axis of Female Rhesus Macaques (Macaca mulatta) Biol Reprod, October 1, 2006; 75(4): 539 - 546. [Abstract] [Full Text] [PDF]

				C. D. Bushnell, P. Hurn, C. Colton, V. M. Miller, G. del Zoppo, M. S.V. Elkind, B. Stern, D. Herrington, G. Ford-Lynch, P. Gorelick, et al. Advancing the Study of Stroke in Women: Summary and Recommendations for Future Research From an NINDS-Sponsored Multidisciplinary Working Group Stroke, September 1, 2006; 37(9): 2387 - 2399. [Abstract] [Full Text] [PDF]

				A. Aviv Telomeres and human somatic fitness. J. Gerontol. A Biol. Sci. Med. Sci., August 1, 2006; 61(8): 871 - 873. [Abstract] [Full Text] [PDF]

				L. Sunday, M. M. Tran, D. N. Krause, and S. P. Duckles Estrogen and progestagens differentially modulate vascular proinflammatory factors Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E261 - E267. [Abstract] [Full Text] [PDF]

				U.H. Lerner Bone Remodeling in Post-menopausal Osteoporosis. J. Dent. Res., July 1, 2006; 85(7): 584 - 595. [Abstract] [Full Text] [PDF]

				U.H. Lerner Bone Remodeling in Post-menopausal Osteoporosis Journal of Dental Research, July 1, 2006; 85(7): 584 - 595. [Abstract] [Full Text] [PDF]

				M. Maggio, J. M. Guralnik, D. L. Longo, and L. Ferrucci Interleukin-6 in aging and chronic disease: a magnificent pathway. J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2006; 61(6): 575 - 584. [Abstract] [Full Text] [PDF]

				I. A. Arenas, Y. Xu, and S. T. Davidge Age-associated impairment in vasorelaxation to fluid shear stress in the female vasculature is improved by TNF-{alpha} antagonism Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1259 - H1263. [Abstract] [Full Text] [PDF]

				A. Aviv, A. Valdes, J. P. Gardner, R. Swaminathan, M. Kimura, and T. D. Spector Menopause Modifies the Association of Leukocyte Telomere Length with Insulin Resistance and Inflammation J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 635 - 640. [Abstract] [Full Text] [PDF]

				M. R. Ryan, R. Shepherd, J. K. Leavey, Y. Gao, F. Grassi, F. J. Schnell, W.-P. Qian, G. J. Kersh, M. N. Weitzmann, and R. Pacifici An IL-7-dependent rebound in thymic T cell output contributes to the bone loss induced by estrogen deficiency PNAS, November 15, 2005; 102(46): 16735 - 16740. [Abstract] [Full Text] [PDF]

				J. J. Puder, S. Varga, M. Kraenzlin, C. De Geyter, U. Keller, and B. Muller Central Fat Excess in Polycystic Ovary Syndrome: Relation to Low-Grade Inflammation and Insulin Resistance J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6014 - 6021. [Abstract] [Full Text] [PDF]

				C. A. O'Brien, R. L. Jilka, Q. Fu, S. Stewart, R. S. Weinstein, and S. C. Manolagas IL-6 is not required for parathyroid hormone stimulation of RANKL expression, osteoclast formation, and bone loss in mice Am J Physiol Endocrinol Metab, November 1, 2005; 289(5): E784 - E793. [Abstract] [Full Text] [PDF]

				M Cutolo, A Sulli, and B Seriolo Estrogens, autoimmunity and the heart Lupus, September 1, 2005; 14(9): 675 - 678. [Abstract] [PDF]

				G. Schonfelder The biological impact of estrogens on gender differences in congestive heart failure Cardiovasc Res, September 1, 2005; 67(4): 573 - 574. [Full Text] [PDF]

				Y. Huang, S. Cao, M. Nagamani, K. E. Anderson, J. J. Grady, and L.-J. W. Lu Decreased Circulating Levels of Tumor Necrosis Factor-{alpha} in Postmenopausal Women during Consumption of Soy-Containing Isoflavones J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 3956 - 3962. [Abstract] [Full Text] [PDF]

				A. P. V. Dantas and K. Sandberg Estrogen Regulation of Tumor Necrosis Factor-{alpha}: A Missing Link Between Menopause and Cardiovascular Risk in Women? Hypertension, July 1, 2005; 46(1): 21 - 22. [Full Text] [PDF]

				E Kassi, P G Vlachoyiannopoulos, A Kominakis, H Kiaris, H M Moutsopoulos, and P Moutsatsou Estrogen receptor alpha gene polymorphism and systemic lupus erythematosus: a possible risk? Lupus, May 1, 2005; 14(5): 391 - 398. [Abstract] [PDF]

				C. L. Speyer, N. J. Rancilio, S. D. McClintock, J. D. Crawford, H. Gao, J. V. Sarma, and P. A. Ward Regulatory effects of estrogen on acute lung inflammation in mice Am J Physiol Cell Physiol, April 1, 2005; 288(4): C881 - C890. [Abstract] [Full Text] [PDF]

				C. J. Jagger, J. M. Lean, J. T. Davies, and T. J. Chambers Tumor Necrosis Factor-{alpha} Mediates Osteopenia Caused by Depletion of Antioxidants Endocrinology, January 1, 2005; 146(1): 113 - 118. [Abstract] [Full Text] [PDF]

				G. M. Leong, S. Moverare, J. Brce, N. Doyle, K. Sjogren, K. Dahlman-Wright, J.-A. Gustafsson, K. K. Y. Ho, C. Ohlsson, and K.-C. Leung Estrogen Up-Regulates Hepatic Expression of Suppressors of Cytokine Signaling-2 and -3 in Vivo and in Vitro Endocrinology, December 1, 2004; 145(12): 5525 - 5531. [Abstract] [Full Text] [PDF]

				Y. Gao, W.-P. Qian, K. Dark, G. Toraldo, A. S. P. Lin, R. E. Guldberg, R. A. Flavell, M. N. Weitzmann, and R. Pacifici Estrogen prevents bone loss through transforming growth factor {beta} signaling in T cells PNAS, November 23, 2004; 101(47): 16618 - 16623. [Abstract] [Full Text] [PDF]

				F. Zheng, Q.-L. Cheng, A.-R. Plati, S. Q. Ye, M. Berho, A. Banerjee, M. Potier, E. A. Jaimes, H. Yu, Y.-F. Guan, et al. The Glomerulosclerosis of Aging in Females: Contribution of the Proinflammatory Mesangial Cell Phenotype to Macrophage Infiltration Am. J. Pathol., November 1, 2004; 165(5): 1789 - 1798. [Abstract] [Full Text] [PDF]

				K.-C. Leung, G. Johannsson, G. M. Leong, and K. K. Y. Ho Estrogen Regulation of Growth Hormone Action Endocr. Rev., October 1, 2004; 25(5): 693 - 721. [Abstract] [Full Text] [PDF]

				D. Pisera, M. Candolfi, S. Navarra, J. Ferraris, V. Zaldivar, G. Jaita, M. G. Castro, and A. Seilicovich Estrogens sensitize anterior pituitary gland to apoptosis Am J Physiol Endocrinol Metab, October 1, 2004; 287(4): E767 - E771. [Abstract] [Full Text] [PDF]

				T. M. Doherty, L. A. Fitzpatrick, D. Inoue, J.-H. Qiao, M. C. Fishbein, R. C. Detrano, P. K. Shah, and T. B. Rajavashisth Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification Endocr. Rev., August 1, 2004; 25(4): 629 - 672. [Abstract] [Full Text] [PDF]

				W.-L. Yang, A. K. Godwin, and X.-X. Xu Tumor Necrosis Factor-{alpha}-Induced Matrix Proteolytic Enzyme Production and Basement Membrane Remodeling by Human Ovarian Surface Epithelial Cells: Molecular Basis Linking Ovulation and Cancer Risk Cancer Res., February 15, 2004; 64(4): 1534 - 1540. [Abstract] [Full Text] [PDF]

				A. J. Krieg, S. A. Krieg, B. S. Ahn, and D. J. Shapiro Interplay between Estrogen Response Element Sequence and Ligands Controls in Vivo Binding of Estrogen Receptor to Regulated Genes J. Biol. Chem., February 6, 2004; 279(6): 5025 - 5034. [Abstract] [Full Text] [PDF]

				S. Cenci, G. Toraldo, M. N. Weitzmann, C. Roggia, Y. Gao, W. P. Qian, O. Sierra, and R. Pacifici Estrogen deficiency induces bone loss by increasing T cell proliferation and lifespan through IFN-{gamma}-induced class II transactivator PNAS, September 2, 2003; 100(18): 10405 - 10410. [Abstract] [Full Text] [PDF]

				E. Vegeto, S. Belcredito, S. Etteri, S. Ghisletti, A. Brusadelli, C. Meda, A. Krust, S. Dupont, P. Ciana, P. Chambon, et al. Estrogen receptor-{alpha} mediates the brain antiinflammatory activity of estradiol PNAS, August 5, 2003; 100(16): 9614 - 9619. [Abstract] [Full Text] [PDF]

				M. C. Carr The Emergence of the Metabolic Syndrome with Menopause J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2404 - 2411. [Abstract] [Full Text] [PDF]

				K.-i. Hirose, H. Tomiyama, R. Okazaki, T. Arai, Y. Koji, G. Zaydun, S. Hori, and A. Yamashina Increased Pulse Wave Velocity Associated with Reduced Calcaneal Quantitative Osteo-sono Index: Possible Relationship Between Atherosclerosis and Osteopenia J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2573 - 2578. [Abstract] [Full Text] [PDF]

				A. Mouihate and Q. J. Pittman Neuroimmune Response to Endogenous and Exogenous Pyrogens Is Differently Modulated by Sex Steroids Endocrinology, June 1, 2003; 144(6): 2454 - 2460. [Abstract] [Full Text] [PDF]

				J.-M. Rakic, V. Lambert, M. Deprez, J.-M. Foidart, A. Noel, and C. Munaut Estrogens Reduce the Expression of YKL-40 in the Retina: Implications for Eye and Joint Diseases Invest. Ophthalmol. Vis. Sci., April 1, 2003; 44(4): 1740 - 1746. [Abstract] [Full Text] [PDF]

				P. Garnero, C. Jamin, C.-L. Benhamou, C. Pelissier, and C. Roux Effects of tibolone and combined 17{beta}-estradiol and norethisterone acetate on serum C-reactive protein in healthy post-menopausal women: a randomized trial Hum. Reprod., October 1, 2002; 17(10): 2748 - 2753. [Abstract] [Full Text] [PDF]