Production of pro- and anti-inflammatory cytokines of human placental trophoblasts in response to pathogenic bacteria

Objective: We studied the production of cytokines in purified cultures of human term trophoblasts in the presence of pathogenic strains of Escherichia coli, Bacteroides fragilis, Mycoplasma hominis, Staphylococcus aureus, and Streptococcus agalactiae, which have been identified in intrauterine infections. Methods: Human villous trophoblasts were isolated from term placentas after cesarean section and purified by several steps. After 6, 12, and 24 hours of incubation with the different heat-inactivated bacteria, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) as well as tumor necrosis factor-α (TNF-α) were measured from supernatants by commercially available enzyme-linked immunosorbent assay. Expression of cytokine mRNAs was determined by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Results: In nonstimulated cultures, low (IL-1β and TNF-α) and high (IL-6, IL-8, and IL-10) basal secretion of cytokines was detectable. The pathogenic microorganisms induced a dose- and time-dependent release of IL-1β, IL-6, IL-8, and IL-10, whereas TNF-α secretion was not elevated. E coli was the most potent inducer followed by B fragilis, S agalactiae, S aureus, and M hominis. Transcripts encoding IL-1β, IL-6, IL-8, or IL-10 were elevated in the RT-PCR reactions, suggesting that transcriptional mechanisms contribute to elevated cytokine expression. Conclusion: Pathogenic microorganisms stimulated mRNA expression and polypeptide release of pro- and anti-inflammatory cytokines from placental trophoblasts. Induction of both inflammation-promoting and inflammation-inhibiting cytokines by bacterial products could play a role in modulating the inflammatory response associated with chorioamnionitis.