47: Diversity in fetal membrane cytokine signature to stimulation by bacterial infections associated with preterm birth


      Immune and biochemical pathways of preterm labor vary in response to specific bacteria associated with intraamniotic infection (IAI) and they also differ between races. We tested normal term fetal membranes exposed to 8 IAI pathogens associated with spontaneous preterm birth (PTB) for differential immune response and racial disparity.

      Study Design

      Fetal membranes collected from African-American (n=5) and Caucasian (n=5) women were placed in an organ explant culture system and pre-incubated for 48 h. Cultures were then stimulated for 24 h with Ureaplasma urealyticum (UU), Ureaplasma parvum (UP), Mycoplasma hominis (MH), E. coli (EC), Group B Streptococci (GBS), Polyporhans gingivalis (PG), Gardnerella vaginalis (GV). Concentrations of IL-1beta, IL-2, IL-8, IL-10 and TNF-alpha in the medium were quantified and analyzed by mixed effects linear models.


      All pathogens significantly increased IL-8 production with no effect on IL-2 production compared to unstimulated controls. EC and GV had the most proinflammatory activity (increased IL-1beta, and TNF-alpha) whereas the minimal immune responses (marginal increase in TNF-alpha) to genital mycoplasmas (UU, UP, and MH) were balanced by increased production of anti-inflammatory IL-10. The immune responses to GBS and the periodontal pathogen PG were limited to one cytokine each (IL-1beta and TNF-alpha, respectively). Only EC demonstrated racial disparity where African-Americans had twice the IL-1beta response as Caucasians (P=0.03). See table below for details.
      Tabled 1
      Table thumbnail grt1


      Pathogens associated with PTB have different cytokine signatures. Pathogens with LPS provoked maximum immune response. Promotion of IL-10 production and limited proinflammatory responses by genital mycoplasmas reflect their adaptation to the unique maternal-fetal environment. Infectious agents such as E. coli may play a role in the racial disparity in infection-mediated PTB. This study reiterates that pathways of IAI associated PTB are not universal. PTB interventions should take into account type of pathogen exposure and subjects race/ethnicity.