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NEUROENDOCRINOLOGY LETTERS
including Psychoneuroimmunology, Neuropsychopharmacology,
Reproductive Medicine, Chronobiology
and Human Ethology, ISSN 0172–780X

NEL Vol.24 Nos.3/4, Jun-Aug 2003

ORIGINAL ARTICLE

Running Title:
Estradiol, Progesterone and Cytokines Production

2003; 24:185191
pii: NEL243403A06
PMID: 14523355

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The effect of estradiol, but not progesterone, on the production of cytokines in stimulated whole blood, is concentration-dependent

Khalid Z. Matalka

Faculty of Pharmacy and Medical Technology, University of Petra, Amman, Jordan.

Submitted: March 3, 2003
Accepted: March 7, 2003

Key words:
estradiol, progesterone, TNF-a, IFN-g, IL-10, IL-12

Abstract

OBJECTIVES: The purpose of this study was to determine the effects of estradiol and progesterone on interferon-g (IFN-g), interleukin (IL)-12, IL-10 and tumor necrosis factor-a (TNF-a) productions in polyclonal activators (phyto­hemagglutinin+lipopolysaccharide)-stimulated whole blood cultures.

METHODS: Nineteen healthy males and females volunteered in the study. Blood samples were drawn, diluted, and cultured for 24h with different concentrations of estradiol, progesterone or hydrocortisone and then PHA+LPS was added for another 24 h. The supernatant, then, was harvested and assayed for IL-12 p70, IFN-g, IL-10 and TNF-a.

RESULTS: At preovulatory concentrations, estradiol enhanced significantly IFN-g, IL-12 and IL-10, but not TNF-a, production levels and reversed the suppressive effect of hydrocortisone in PHA+LPS stimulated whole blood. While IL-10 levels kept increasing at pregnancy estradiol concentrations, IFN-g, IL-12 levels and IFN-g/IL-10 ratio decreased significantly. No effect of progesterone on IL-12 p70, IFN-g, IL-10 and TNF production levels was observed.

CONCLUSIONS: The present study shows that those pregnancy estradiol concentrations (and higher) enhance the production of IL-10 and reduce IL-12, IFN-g levels and IFN-g/IL-10 ratio in stimulated whole blood cells. Because of the known IL-10 inhibitory actions on T helper (Th) 1 cells and monocytes/macrophages, these high IL-10 levels keep Th2 cytokines favored during pregnancy and may be useful in shifting Th1-mediated autoimmune diseases towards non-pathogenic Th2 pathway.

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Society of Integrated Sciences
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