Influence of progesterone on functional activity of neutrophils in threatening preterm labor

Abstract

Aim of the study. To assess the influence of exogenous progesterone on the functional activity of neutrophils in patients, whose pregnancies proceeded with clinical signs of threatened abortion. Materials and methods. The material used for the study were peripheral blood neutrophils of 32 women, who were hospitalized with a diagnosis of "threatening premature labor" in the term of 22-34 weeks and whose pregnancies later ended in spontaneous preterm (group 1, 10 patients) and term (group 2, 22 patients) birth. Women of 1st and 2nd groups were comparable in age, gestational age and serum concentration of endogenous progesterone. The study was conducted in vitro. Neutrophils were isolated by settling for NBT-test and phagocytosis reaction, and by centrifugation on a double density gradient of ficoll-verografin in order to assess the formation of neutrophil extracellular traps. Neutrophils were added to a suspension of exogenous progesterone at concentrations of 10 ng/ml, 20 ng/ml, 100 ng/ml. The oxidation activity of neutrophils was measured in the spontaneous and stimulated (with Staphylococcus aureus at a concentration of 1×108 bacterial cells in 1 ml) types of NBT-test with microscopic evaluation of the results. The ability of neutrophils to form extracellular traps was evaluated in spontaneous and stimulated (with Staphylococcus aureus at a concentration of 1×108 bacterial cells in 1 ml) types of the test using color dye Hoechst 33342, followed by fluorescent microscopy. Results. Progesterone (10 ng/ml) significantly decreased spontaneous neutrophil oxidative activity [17.0% (12.0-26.0%) and 7.0% (4.0-10.0%), p<0.05] in patients of group 1, but not in patients of group 2. There was no effect of progesterone at studied concentrations on stimulated neutrophil oxidative activity in women of groups 1 and 2. When 20 ng/ml progesterone was added there was a decrease in neutrophil phagocytic index in patients of group 2 [66% (55-77%) and 51% (40-69%), p<0.05]. Progesterone (100 ng/ml) caused an increase in spontaneous NET-forming function in both groups and had no effect on stimulated function. Conclusions. Progesterone is able to provide various immunomodulatory effects on neutrophils of patients, whose pregnancies ended in preterm and term birth. Exogenous progesterone is able to provide various immunomodulatory effects on neutrophils of patients, whose pregnancies ended in preterm and term birth. It reduced the increased spontaneous oxidative activity of neutrophils in women with adverse pregnancy outcomes and lowered phagocytic number in patients with favorable pregnancy outcome. This drug also stimulated spontaneous NET-forming function of the cells, regardless of the pregnancy outcome.