Possible Roles of Proinflammatory and Chemoattractive Cytokines Produced by Human Fetal Membrane Cells in the Pathology of Adverse Pregnancy Outcomes Associated with Influenza Virus Infection

Abstract

Pregnant women are at an increased risk of influenza-associated adverse outcomes, such as premature delivery, based on data from the latest pandemic with a novel influenza A (H1N1) virus in 2009-2010. It has been suggested that the transplacental transmission of influenza viruses is rarely detected in humans. A series of our study has demonstrated that influenza virus infection induced apoptosis in primary cultured human fetal membrane chorion cells, from which a factor with monocyte differentiation-inducing (MDI) activity was secreted. Proinflammatory cytokines, such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-β, were identified as a member of the MDI factor. Influenza virus infection induced the mRNA expression of not only the proinflammatory cytokines but also chemoattractive cytokines, such as monocyte chemoattractant protein (MCP)-1, regulated on activation, normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1β, IL-8, growth-regulated oncogene (GRO)-α, GRO-β, epithelial cell-derived neutrophil-activating protein (ENA)-78, and interferon inducible protein (IP)-10 in cultured chorion cells. These cytokines are postulated to associate with human parturition. This paper, therefore, reviews (1) lessons from pandemic H1N1 2009 in pregnancy, (2) production of proinflammatory and chemoattractive cytokines by human fetal membranes and their functions in gestational tissues, and (3) possible roles of cytokines produced by human fetal membranes in the pathology of adverse pregnancy outcomes associated with influenza virus infection.

Pregnancy outcome and clinical status of gilts following experimental infection by H1N2, H3N2 and H1N1pdm09 influenza A viruses during the last month of gestation

“…Abortions in influenza A virus (IAV)-infected humans as well as animals, including pigs, seem to be a result of high fever and a ''cytokine storm'' associated with acute infection, but transplacental transmission of the virus has been also reported [5][6][7][8][9][10]. Influenza virus has also been isolated from amnion and chorion tissues in guinea pigs [11] and amniotic fluid in ferrets [12]. To date, there is insufficient data to conclude that IAV has a specific and direct association with the occurrence of reproductive problems.…”

Review on the effects of influenza vaccination during pregnancy on preterm births

“…2,11 The adverse fetal effects of influenza infection during pregnancy could be due to a direct biological effect of maternal viral infection in the fetus, or secondary to influenza illness stimulating an inflammatory response which could include an increase in prostaglandin E and other cytokine and chemokine production that could precipitate labor. 12 On the same note influenza infection normally presents with fever and it has been shown that hyperthermia during pregnancy is associated with an increased risk for certain birth defects and birth adverse outcomes. 13 Congenital transmission of influenza virus from mother to fetus in utero has been reported to be an infrequent phenomenon.…”

Influenza immunization during pregnancy: Benefits for mother and infant

“…The state of relative immunosuppression during pregnancy and early life may contribute to increased susceptibility to infectious diseases and not surprisingly, pregnant women and newborns have been shown to be at increased risk of influenza complications including hospitalization, intensive care unit admission and death. [1][2][3][4] A US study showed that of pregnant women hospitalized with pandemic H1N1/2009 pdm infection, 22.6% required admission to intensive care units. 3 Similarly, during previous influenza pandemics in 1918/1919 and 1957/1958 mortality rates were considerably higher among pregnant women than in the general population, in addition to a high rate of pregnancy loss.…”