Production of Proinflammatory Cytokines by Syncytiotrophoblasts Infected with Human Cytomegalovirus Isolates

Forty per cent of women with primary cytomegalovirus (CMV) infection during gestation transmit the infection to their fetuses, which may result in abnormalities for the newborn, varying in degree from mild to severe. The factors whereby CMV in the placenta develops into a fulminating infection and spreads to the fetus are not known. In this study the production of proinflammatory cytokines was investigated in syncytiotrophoblast (ST) cultures infected with CMV strains. The interrelationships between the cytokines produced in the ST cultures and the number of nuclei of ST expressing the CMV immediate-early (IE) gene were examined. To resemble a natural infection, clinical CMV isolates and a low multiplicity of infection were used. TNF-α and IL-1β were not detected in the supernatants of any ST cultures. Similar or increased amounts of IL-6 were found in the CMV-infected cultures. The IL-8-inducing capacities of the CMV strains differed in the ST cultures. The IE gene expression of the virus provided was dependent on the amount of IL-8 produced in the STs. Our observations indicate that certain CMV strains induce high amounts of IL-8, which in turn enhances CMV replication in the placenta, while others can replicate if the IL-8 is provided by a co-infecting agent.