Effects of estradiol and progesterone on the proinflammatory cytokine production by mononuclear cells from patients with chronic hepatitis C.
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.
Yuan
Ying
Y
Department of Digestive and Cardiovascular Medicine, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto-cho, Tokushima 7708503, Japan.
Shimizu
Ichiro
I
Shen
Mi
M
Aoyagi
Eriko
E
Takenaka
Hidetaka
H
Itagaki
Tatuzo
T
Urata
Mari
M
Sannomiya
Katsutaka
K
Kohno
Nao
N
Tamaki
Katsuyoshi
K
Shono
Masayuki
M
Takayama
Tetsuji
T
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*
D016207:Cytokines; D011374:Progesterone; D004958:Estradiol