title: Hormonal modulation of interleukin-6, tumor necrosis factor and associated receptor secretion in postmenopausal women.
abstract: Hormone replacement therapy (HRT) reduces the risk for osteoporosis but transiently increases cardiovascular risk for some postmenopausal women. This study investigated the hypothesis that these risks are associated with HRT-induced changes in mononuclear cell secretion of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and associated soluble receptors. Compared to the untreated condition (n=8), estrogen therapy (n=7) and estrogen+progestin therapy (n=7) both caused 2-fold elevations in TNF-alpha secretion. IL-6 secretion was increased (48%, P=0.04) only by estrogen+progestin therapy. Although soluble receptor secretion was not different among groups, soluble TNF receptor type I and IL-6 receptor secretion were inversely related to plasma follicle stimulating hormone (P<0.05). Both therapies reduced plasma osteocalcin (a marker for osteoporosis) by approximately 50% (P<0.002). Plasma C-reactive protein (CRP, a marker for cardiovascular risk) was 3-fold higher in women receiving only estrogen, compared to untreated women (P=0.01), and twice as high as those receiving estrogen+ progestin (P=0.045). Simple linear relationships were not observed between cytokine secretion and these markers, but a significant HRT/TNF-alpha interaction with osteocalcin (P=0.022) and an HRT/IL-6 interaction with CRP (P =0.016) indicated more complex relationships between hormone replacement, cytokine activity, and health risks associated with menopause.
authors.affiliation: Noll Physiological Research Center, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Esther M
authors.initials: EM
authors.lastname: Brooks-Asplund
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Tupper
authors.forename: Jane M
authors.initials: JM
authors.lastname: Daun
authors.forename: W Larry
authors.initials: WL
authors.lastname: Kenney
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Cannon
mesh_terms: D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004338:Drug Combinations; D004967:Estrogens / Q000494:pharmacology; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D020249:Hormone Replacement Therapy; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D015675:Osteocalcin / Q000097:blood / Q000378:metabolism; D017698:Postmenopause; D011372:Progestins / Q000494:pharmacology; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016207:Cytokines; D004338:Drug Combinations; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D015850:Interleukin-6; C466383:Prempro; D011372:Progestins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D015675:Osteocalcin; D005640:Follicle Stimulating Hormone; D002097:C-Reactive Protein; D017258:Medroxyprogesterone Acetate