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Effects of estradiol and progesterone on the proinflammatory cytokine production by mononuclear cells from patients with chronic hepatitis C

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World Journal of Gastroenterology 2008年第14期14卷 2200-2207页

作者： Ying Yuan Ichiro Shimizu Mi Shen Eriko Aoyagi hidetaka takenaka Tatuzo Itagaki Mari Urata Katsutaka Sannomiya Nao Kohno Katsuyoshi Tamaki Masayuki Shono Tetsuji Takayama Jiangsu Key Laboratory of Neuroregeneration Nantong University Nantong 226001 Jiangsu Province China Department of Digestive and Cardiovascular Medicine Institute of Health Biosciences Tokushima 7708503 Japan Support Center for Advanced Medical Sciences University of Tokushima Graduate School Tokushima 7708503 Japan

AIM:To investigate the effects of estradiol (E2) and progesterone on the unstimulated and oxidative stressstimulated production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, and macrophage chemotactic protein (MCP)-1 by peripheral blood mononuclear cells (PBMCs) from patients with chronic hepatitis C and healthy controls. METHODS:The PBMCs were separated from agematched 72 males and 71 females with and without chronic hepatitis C, who were divided into two groups based on a mean menopausal age of 50 years. Oxidative stress was induced by hydrogen peroxide in the cells incubated in serum-free media. Cytokines in the culture supernatant were measured by an enzyme-linked immunosorbent assay. RESULTS:The highest levels of the spontaneous production of TNF-α, IL-1β, IL-8, and MCP-1 by the unstimulated PBMCs were in the older male patients with chronic hepatitis C and the lowest levels were in the premenopausal female healthy controls. E2 inhibited the cytokine production by the unstimulated PBMCs from the older male and post-menopausal female patients, which was further stimulated by progesterone. The exposure to hydrogen peroxide in the PBMCs from the younger male and pre-menopausal female healthy subjects induced the production of cytokines. The change rates of the hydrogen peroxide-stimulated cytokine production were suppressed by E2 and enhanced by progesterone. CONCLUSION:These findings suggest that E2 may play a favorable role in the course of persistent liver injury by preventing the accumulation of monocytes-macrophages and by inhibiting proinflammatory cytokine production, whereas progesterone may counteract the favorable E2 effects.

关键词： Estradiol Progesterone Mononuclear cell Proinflammatory cytokine Chemokine

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