Changes in serum cytokine concentrations during the menopausal transition

Yasui, Toshiyuki; Murakami, Masahiko; Tomita, Junko; Miyatani, Yuka; Yamada, Masayo; Uemura, Hirokazu; Matsuzaki, Takashi; Kuwahara, Akira; Kamada, Masao; Tsuchiya, Naho; Yuzurihara, Mitsutoshi; Takeda, Susumu; Irahara, Minoru

doi:10.1016/j.maturitas.2006.11.002

Cited by 105 publications

(95 citation statements)

References 23 publications

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“…Another group in Japan investigated changes in the serum of cytokines among 122 pre-, peri-and postmenopausal women. They reported a positive correlation of IL-6 with age, in addition to significant increases in IL-2, GM-CSF, G-CSF and IL-4 in postmenopausal women [31]. We observed a trend towards an increase in IL-4 with age, but this was non-significant.…”

Section: All Subjectscontrasting

confidence: 62%

Normal ageing is associated with an increase in Th2 cells, MCP-1 (CCL1) and RANTES (CCL5), with differences in sCD40L and PDGF-AA between sexes

Mansfield¹,

Nevala²,

Dronca³

et al. 2012

Clinical and Experimental Immunology

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SummaryWe have observed T helper type 2 (Th2) polarization of systemic immunity in patients with metastatic malignant melanoma. We hypothesized that similar changes in systemic immunity occur with ageing and may be permissive for the development of melanoma. We analysed the peripheral blood of 389 healthy blood donors. All subjects were profiled for peripheral blood T cell and B cell subsets, and 58 of these subjects were profiled for antigen-specific cytotoxic T cell subsets [cytomegalovirus (CMV), influenza and melanoma antigen recognized by T cells 1 (MART-1)]. Ninety-five separate healthy subjects underwent profiling of 42 plasma cytokines. Ageing was associated positively with CD4 + CD294 + Th2 cells, and associated negatively with CD3 + T cells, cytotoxic T cells and T helper cells. Ageing was also associated negatively with CMV-, influenza-and MART-1-specific naive and CD8+ T cells. There were significant increases in plasma monocyte chemotactic protein 1 (MCP-1) (CCL1) and regulated upon activation normal T cell expressed and secreted (RANTES) (CCL5) with age. We observed differences in cytokine profiles between males and females; specifically, women had higher levels of sCD40L and PDGF-AA. In summary, we demonstrated in healthy blood donors that ageing was associated with an increase in cellular Th2 bias and a decline in total numbers of T cells. Additionally, there was an increase in MCP-1 and RANTES with ageing. Women had higher levels of sCD40L and PDGF-AA than men.

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Section: All Subjectscontrasting

confidence: 62%

Normal ageing is associated with an increase in Th2 cells, MCP-1 (CCL1) and RANTES (CCL5), with differences in sCD40L and PDGF-AA between sexes

Mansfield¹,

Nevala²,

Dronca³

et al. 2012

Clinical and Experimental Immunology

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“…Log serum IL-6 (pg/mL) Log unstimulated PBMC IL-6 (pg/mL) 1990;Yasui et al 2007). Therefore, circulating IL-6 levels may be a better marker of chronic low-grade inflammatory activity in aging individuals, particularly in older postmenopausal women than systemic levels of TNF-α and IL-1β.…”

Section: Discussionmentioning

confidence: 99%

Effects of aging and menopause on serum interleukin-6 levels and peripheral blood mononuclear cell cytokine production in healthy nonobese women

Kim

Chae

Paik

et al. 2011

AGE

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Inappropriate interleukin-6 production is thought to play a role in the development of several age-related conditions including atherosclerosis. This study aimed to determine whether aging affects circulating interleukin-6 (IL-6) levels. Healthy, nonobese women (n = 208, 44.5 ± 0.70 years, 22.4 ± 0.17 kg/m 2 ) were categorized into four age groups (22-31, 32-41, 42-51, and 52-63 years; crosssectional study). Cytokine levels in serum and those produced from peripheral blood mononuclear cell (PBMC) were measured. The oldest group had the highest circulating levels of IL-6 and oxidized lowdensity lipoprotein (ox-LDL) and higher PBMC production of IL-6, tumor necrosis factor-α (TNF-α), and interleukin-1 alpha (IL-1β). Additionally, significant interactions between age and menopause were found for serum IL-6 (P=0.024), and TNF-α (P= 0.011) and IL-1β (P<0.001) produced from PBMCs. Serum IL-6 levels positively correlated with age, waist-hip ratio (WHR), systolic blood pressure, circulating levels of TNF-α, IL-1β, and ox-LDL, and urinary 8-epi-prostaglandin F 2 α. Multiple stepwise AGE (2012) 34:415-425

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“…The elevated cytokine levels likely contribute to the increased incidence of inflammatory diseases after menopause, such as osteoporosis, and neurodegenerative and cardiovascular diseases (3)(4)(5)(6). Because estrogens are known to have antiinflammatory properties (2), and estrogens in the form of hormone therapy (HT) 3 lower cytokine levels in postmenopausal women (2,7), it seems practical to attempt to prevent inflammatory diseases associated with menopause by replacing estrogens after the onset of menopause. Observational studies supported this rationale for using HT as a chemopreventative intervention by showing that HT decreased osteoporosis, Alzheimer's disease, and cardiovascular disease (8 -10).…”

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confidence: 99%

Selective Estrogen Receptor-β Agonists Repress Transcription of Proinflammatory Genes

Čvoro

Tatomer

Tee

et al. 2008

The Journal of Immunology

124

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In addition to their role in the development and function of the reproductive system, estrogens have significant anti-inflammatory properties. Although both estrogen receptors (ERs) can mediate anti-inflammatory actions, ERβ is a more desirable therapeutic target because ERα mediates the proliferative effects of estrogens on the mammary gland and uterus. In fact, selective ERβ agonists have beneficial effects in preclinical models involving inflammation without causing growth-promoting effects on the uterus or mammary gland. However, their mechanism of action is unclear. The purpose of this study was to use microarray analysis to determine whether ERβ-selective compounds produce their anti-inflammatory effects by repressing transcription of proinflammatory genes. We identified 49 genes that were activated by TNF-α in human osteosarcoma U2OS cells expressing ERβ. Estradiol treatment significantly reduced the activation by TNF-α on 18 genes via ERβ or ERα. Most repressed genes were inflammatory genes, such as TNF-α, IL-6, and CSF2. Three ERβ-selective compounds, ERB-041, WAY-202196, and WAY-214156, repressed the expression of these and other inflammatory genes. ERB-041 was the most ERβ-selective compound, whereas WAY-202196 and WAY-214156 were the most potent. The ERβ-selective compounds repressed inflammatory genes by recruiting the coactivator, SRC-2. ERB-041 also repressed cytokine genes in PBMCs, demonstrating that ERβ-selective estrogens have anti-inflammatory properties in immune cells. Our study suggests that the anti-inflammatory effects of ERB-041 and other ERβ-selective estrogens in animal models are due to transcriptional repression of proinflammatory genes. These compounds might represent a new class of drugs to treat inflammatory disorders.

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Changes in serum cytokine concentrations during the menopausal transition

Cited by 105 publications

References 23 publications

Normal ageing is associated with an increase in Th2 cells, MCP-1 (CCL1) and RANTES (CCL5), with differences in sCD40L and PDGF-AA between sexes

Normal ageing is associated with an increase in Th2 cells, MCP-1 (CCL1) and RANTES (CCL5), with differences in sCD40L and PDGF-AA between sexes

Effects of aging and menopause on serum interleukin-6 levels and peripheral blood mononuclear cell cytokine production in healthy nonobese women

Selective Estrogen Receptor-β Agonists Repress Transcription of Proinflammatory Genes

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