title: Effects of estradiol and progesterone on the proinflammatory cytokine production by mononuclear cells from patients with chronic hepatitis C.
abstract: OBJECTIVE
  To investigate the effects of estradiol (E2) and progesterone on the unstimulated and oxidative stress-stimulated production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, 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 age-matched 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-alpha, IL-1beta, 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 pre-menopausal 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Digestive and Cardiovascular Medicine, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto-cho, Tokushima 7708503, Japan.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yuan
authors.forename: Ichiro
authors.initials: I
authors.lastname: Shimizu
authors.forename: Mi
authors.initials: M
authors.lastname: Shen
authors.forename: Eriko
authors.initials: E
authors.lastname: Aoyagi
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Takenaka
authors.forename: Tatuzo
authors.initials: T
authors.lastname: Itagaki
authors.forename: Mari
authors.initials: M
authors.lastname: Urata
authors.forename: Katsutaka
authors.initials: K
authors.lastname: Sannomiya
authors.forename: Nao
authors.initials: N
authors.lastname: Kohno
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Tamaki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shono
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takayama
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D017698:Postmenopause; D017697:Premenopause; D011374:Progesterone / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D011374:Progesterone; D004958:Estradiol