Studies in humans and in animal models have linked HCA, a neutrophil
(PMN)-driven placental disorder associated with increased Th17 responses, with
exaggerated inflammatory responses of both innate and adaptive immune cells.
Neutrophil (PMN) production and activation may be increased, along with the
release of inflammatory cytokines and chemokines that promote PMN infiltration
and injury to major organs. Experimental fetal inflammation can induce
functional maturation and activation of monocytes (Mono) and macrophages (Macs)
that can also heighten inflammatory responses. Fetal inflammation enhances the
generation of inflammatory Th17 cells and IL-17+ Treg cells; while IL-17 is
important to host protection, high levels can induce organ injury, particularly
in the brain. Exaggerated inflammatory responses may lead to suppression of
protective immune responses, which increase risk for infection. Neonatal
infection in the context of HCA exposure has also been shown to increase risk
for organ injury and has been linked to bronchopulmonary dysplasia.