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Objective: The aim of the present study was to determine the associations of interleukin (IL)-6 with other cytokines and chemokines and to compare these associations in peri- and postmenopausal women., Methods: Ninety-nine perimenopausal and 92 postmenopausal women were enrolled in this study. Serum concentrations of IL-6, IL-1beta, IL-2, IL-4, IL-5, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, tumor necrosis factor (TNF)-alpha, interferon gamma, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage (GM)-CSF, macrophage inflammatory protein (MIP)-1beta and monocyte chemotactic protein (MCP)-1 were measured simultaneously using a multiplexed cytokine assay., Results: Among the 17 cytokines, IL-6, IL-1beta, IL-5, IL-7, IL-8, IL-10, MCP-1 and MIP-1beta were detected in serum in more than 50% of the women. Serum levels of IL-4 and MCP-1 in postmenopausal women were significantly higher than those in perimenopausal women. Serum IL-6 concentrations showed significant and positive correlations with serum concentrations of IL-1beta, IL-8, MIP-1beta, IL-7 and MCP-1 in women regardless of menopausal status, and these correlations were still significant after adjustment for age and body mass index., Conclusion: Serum IL-6 concentration was found to be closely associated with serum concentrations of IL-1beta, IL-8, MIP-1beta, IL-7 and MCP-1 in women regardless of menopausal status, suggesting that these cytokines act in concert with the progression of several symptoms and various diseases.

Estrogens play important roles in the development of breast cancer. Inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) exist at high concentrations in breast cancer tissue. Although these cytokines are thought to exert some effect on cancer growth, their precise mechanism is still unclear. In the present study, we investigated the effects of inflammatory cytokines on aromatase (Arom) and steroid sulfatase (STS), which are estrogen-producing enzymes, and cell proliferation using human breast cancer cell lines (SK-BR-3, MCF-7). IL-6 and IL-1 beta stimulated the activity of Arom and STS. Estrone sulfate (E1-S) had a stimulus effect on cell proliferation of MCF-7. Although IL-6 did not show significant effect on cell proliferation, cell proliferation was significantly increased when IL-6 and E1-S were simultaneously added to the incubation medium. This cell proliferative effect was apparently stronger than the addition of E1-S alone. Addition of IL-1 beta in the presence of E1-S also significantly enhanced cell proliferation though IL-1 beta alone did not show any effect. These results led us to the hypothesis that inflammatory cytokines such as IL-6 and IL-1 beta regulate proliferation of breast cancer cells through estrogen production by steroid-catalyzing enzymes in the tissue.

Abstract: Objective: The aim of the present study was to compare the effects on serum cytokine concentrations of paroxetine, a selective serotonin re-uptake inhibitor, and kamishoyosan, a Japanese traditional medicine, in midlife women with psychological symptoms. Methods: Seventy-six women with psychological symptoms such as anxiety and mild depression as menopausal symptoms were enrolled in this study. Thirty-eight women received oral administration of 10mg paroxetine every day, and 38 women received oral administration of kamshoyosan every day for 6 months. Overall climacteric symptoms were assessed using Greene''s climacteric scale. Serum levels of cytokines were measured using a multiplexed human cytokine assay. Results: Greene''s total scores in both women treated with paroxetine and in women treated with kamishoyosan decreased significantly. Percentage decreases in Greene''s total, psychological and vasomotor scores during the 6-month period in the paroxetine group were significantly greater than those in the kamishoyosan group. Serum IL-6 concentration in women treated with paroxetine decreased significantly. Serum concentrations of IL-8, IL-10, macrophage inflammatory protein (MIP)-1β and monocyte chemoattractant protein-1 in women treated with paroxetine decreased significantly. On the other hand, serum IL-6 concentration in women treated with kamishoyosan decreased significantly, but other serum concentrations did not change significantly. Conclusion: Decrease in IL-6 concentration may be involved in the mechanism of the actions of both paroxetine and kamishoyosan in women with psychological symptoms, and IL-6 may therefore be useful as a marker of treatment. The action of paroxetine may also be associated with decreases in IL-8, IL-10, MIP-1β. [Copyright &y& Elsevier]

Abstract: Objective: The purpose of the present study was to clarify the association of serum cytokine concentrations, determined using a multiplexed cytokine assay, with psychological symptoms in midlife women. Methods: Fifty-three peri- and post-menopausal women with and without psychological symptoms in Greene''s climacteric scale were enrolled in this study. Levels of 17 cytokines in serum samples were measured simultaneously using a multiplexed human cytokine assay. Results: Serum interleukin (IL)-6 concentration in women with psychological symptoms (2.71±047pg/ml) was significantly (p =0.009) higher than that in women without psychological symptoms (0.98±0.18pg/ml). Serum IL-8 concentration in women with psychological symptoms (33.4±8.17pg/ml) was also significantly (p =0.022) higher than that in women without psychological symptoms (7.87±1.64pg/ml). In addition, serum IL-10 concentration in women with psychological symptoms (0.74±0.26pg/ml) was significantly (p =0.048) higher than that in women without psychological symptoms (0.07±0.04pg/ml). Tumor necrosis factor (TNF)-α in serum was detected only in women with psychological symptoms. Serum IL-2 concentration in women with psychological symptoms tended (p =0.066) to be higher than that in women without psychological symptoms. No significant differences were found between levels of other cytokines in women with and without psychological symptoms. Conclusion: Psychological stress manifested as climacteric symptoms in midlife women may be associated with increases in serum concentrations of IL-6, IL-8, IL-10, and TNF-α. [Copyright &y& Elsevier]