Hyaluronan modulates pro-inflammatory immune activity in the mid-trimester amniotic cavity

Hyaluronan (HA), which comprises repeating disaccharides of D-glucuronic acid and N-acetyl-glucosamine, is a component of the extracellular matrix. In response to infection or tissue injury HA is released into the extracellular milieu where it modulates immune activity. We hypothesized that HA is present in mid-trimester amniotic fluid and contributes to immune regulation at that site. Amniotic fluid from 392 women undergoing a mid-trimester amniocentesis were tested for HA by ELISA. Amniotic fluids from 41 women were also cultured ex vivo in the presence or absence of lipopolysaccharide (LPS). Supernatants were collected after 24 h and tested for tumor necrosis factor-α (TNFα) and interleukin (IL)-10 by ELISA. Clinical parameters were obtained after completion of laboratory testing. All amniotic fluids were positive for HA. The median (range) concentration was 3.2 (0.6-91.7) μg/mg amniotic fluid protein. Women with at least 2 prior pregnancies and a history of ≥2 spontaneous abortions had a higher median HA concentration than did previously pregnant women with 0-1 prior abortions. Women who conceived following in vitro fertilization also had an elevated median amniotic fluid HA compared to women with spontaneous conceptions. Both endogenous and LPS-induced TNFα production by ex vivo cultured amniotic fluid cells, but not IL-10 production, was inversely proportional to the amniotic fluid HA concentration. In conclusion, intraamniotic HA levels are elevated in pregnancies at risk for adverse outcome and HA may be a component of the fetal response to immune alterations that threaten gestation.