Stress-induced versus preovulatory and pregnancy hormonal levels in modulating cytokine production following whole blood stimulation.

Estradiol, progesterone, prolactin and cortisol concentrations are substantially increased during pregnancy. Also, cortisol and prolactin levels are elevated during stress. In the present study, we exposed peripheral blood to estradiol, progesterone, prolactin and cortisol alone or in combination for 24 h before stimulation with T-dependent (phytohemagglutinin, PHA) and independent activators (lipopolysaccharide, LPS) to study their immunomodulatory role in interleukin-12 (IL-12), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and IL-10 production in a whole blood model. This should be similar to in vivo exposure conditions such as long-term stress, preovulatory or pregnancy periods. The present study showed that the stress-induced and preovulatory levels of prolactin and estradiol, respectively, increased the production of IFN-gamma and IL-12 levels (and IL-10 in the case of estradiol) in PHA + LPS-stimulated whole blood, and inhibited a hydrocortisone (100 nmol/l) suppressive effect on IFN-gamma, IL-12 and IL-10 productions. In LPS-stimulated whole blood, however, prolactin enhanced only IL-10 production levels in a non-concentration-dependent manner. Higher prolactin levels as in pregnancy did not modulate any of the cytokines, but pregnancy estradiol concentrations only induced higher IL-10 levels in PHA + LPS-stimulated whole blood. All progesterone levels tested revealed no effect on any of the cytokines following whole blood stimulation. Our results indicate that (1) a long exposure time of prolactin and estradiol to whole blood modulates the production of cytokines in a concentration- and stimulus-dependent manner; (2) stress-induced levels of prolactin and preovulatory estradiol concentrations can regulate cortisol-induced cytokine suppression, and (3) even though the cytokine pattern is different, pregnancy estradiol and cortisol levels decreased the IFN-gamma/IL-10 ratio, thereby keeping the anti-inflammatory IL-10 levels favored during pregnancy, which could be useful in regulating inflammatory-mediated autoimmune diseases.