Intramuscular 17α-hydroxyprogesterone caproate administration attenuates immunoresponsiveness of maternal peripheral blood mononuclear cells.

Abstract

17α-hydroxyprogesterone caproate (17P) may decrease risk of prematurity by suppressing maternal immunity. We hypothesized that in vivo 17P treatment attenuates immunoresponsiveness of peripheral blood mononuclear cells (PBMCs). Study subjects were gravidas receiving weekly prophylactic intramuscular 17P injections. Peripheral blood samples were obtained at 21-27 weeks' gestation. Gestational age-matched, drug-naïve gravidas served as controls. To simulate infection, isolated PBMCs were stimulated with lipoteichoic acid (LTA) or lipopolysaccharide (LPS). Extracellular interleukin-6 (IL-6) concentrations were quantified by an enzyme-linked immunosorbent assay. Unstimulated IL-6 levels were comparable in PBMCs derived from drug-naïve and 17P-treated subjects. LPS and LTA induced a dose-dependent elevation of IL-6 in control PBMCs. In patients who received exogenous 17P, LPS, and LTA stimulated induction of IL-6 was significantly decreased compared with controls (P = .005 and P = .02). In vivo 17P attenuated immunoreactivity of PBMCs in our in vitro model of Gram-positive and Gram-negative bacterial infection.