Influenza virus
infection during pregnancy has been implicated as one of cause of premature delivery, abortion and
stillbirth. We have reported that cultured human fetal membrane chorion cells undergoing apoptosis by influenza virus
infection secrete unidentified heat-stable monocyte differentiation-inducing (MDI) factors. In this study, cellular,
biological and immunochemical characteristics of MDI factors were investigated using human monocytic
leukemia THP-1 cells by
nitroblue tetrazolium reduction and cell adhesion assays. The treatment of THP-1 cells with culture supernatants from the influenza virus-infected chorion cells induced the
nitroblue tetrazolium reduction ability, which was inhibited by the addition of
superoxide dismutase and
diphenyleneiodonium chloride, an inhibitor for reduced
nicotinamide adenine dinucleotide phosphate oxidase. The phenomenon was also observed in human peripheral blood monocytes and histiocytic
leukemia U937 cells, but not in promyelocytic
leukemia HL-60 cells. The induction of
nitroblue tetrazolium reduction and adhesion abilities in THP-1 cells was closely correlated with the concentrations of
interleukin-6 protein in the culture supernatants. These abilities were inhibited to approximately 60% by the addition of
antibodies against
interleukin-6, or alpha-chain (gp80) or beta-chain (gp130) of
IL-6 receptor. The induction of
nitroblue tetrazolium reduction was increased by the addition of supernatants from amniochorion tissue cultures after influenza virus
infection. These results indicate that chorion cell-derived
interleukin-6 is partly responsible for monocyte differentiation to macrophages capable of generating
superoxide anion. It is possible that these pathways represent part of the mechanism for birth complications associated with intrauterine
influenza infection in pregnancy.