Secretion of Bioactive Interleukin-6 and Tumor Necrosis Factor-α Proteins from Primary Cultured Human Fetal Membrane Chorion Cells Infected with Influenza Virus

Influenza virus infection during pregnancy is implicated in one of the causes of premature delivery, abortion and stillbirth. Pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α produced by fetal membranes, are postulated to facilitate premature delivery. We investigated the secretion of IL-6 and TNF-α from primary cultured human fetal membrane chorion and amnion cells infected with influenza virus at protein and bioactivity levels in order to understand the pathology of premature delivery during influenza virus infection. Concentrations of IL-6 and TNF-α proteins were significantly increased in culture supernatants of chorion cells by influenza virus infection. Culture supernatants of the virus-infected chorion cells stimulated the proliferation of IL-6-sensitive 7-TD-1 cells and induced the cytolysis of TNF-α-sensitive L929 cells, both activities of which were inhibited by the addition of respective antibody, whereas no such phenomena were observed in amnion cells. The results demonstrated that only chorion cells secreted significant amounts of bioactive IL-6 and TNF-α proteins responding to influenza virus infection. The present study suggests a possibility that the secretion of bioactive IL-6 and TNF-α proteins from fetal membrane chorion cells is implicated in the pathogenesis of premature delivery during influenza virus infection.