The presence of maternal asthma during pregnancy suppresses the placental pro-inflammatory response to an immune challenge in vitro

Abstract

The mechanisms that contribute to adverse outcomes for the neonate in pregnancies complicated by asthma may be mediated via changes in placental immune function. This study was designed to determine whether the presence of maternal asthma during pregnancy alters the placental pro-inflammatory immune response in vitro. A prospective cohort study of women with asthma (n = 22) and control (n = 11) subjects had placentae collected immediately after delivery. Placental explants were exposed to an immune challenge, lipopolysaccharide, in the presence and absence of cortisol in vitro. Cytokines, glucocorticoid receptor α (GR α) and p38 MAPK protein were measured. Placentae of control pregnancies had an increase in pro-inflammatory cytokine production over a 24 h period. Placentae from pregnancies complicated by maternal asthma had a reduced pro-inflammatory cytokine response to an immune challenge relative to the controls especially in relation to the production of interleukin (IL)-1β and TNFα regardless of fetal sex. Cortisol inhibition of placental cytokine production was dependent on timing of exposure, fetal sex and presence and absence of asthma. GRα and p38 MAPK protein expression did not appear to contribute to differences in response to endotoxin or cortisol. Maternal asthma during pregnancy induces a hyposensitive inflammatory state in the placenta which is regulated by cortisol in a sexually dimorphic manner.