Do Cytokines Contribute to the Andean-Associated Protection From Reduced Fetal Growth at High Altitude?

Pro-versus anti-inflammatory cytokine balance is important for successful pregnancy. Chronic hypoxia alters cytokine levels and increases the frequency of fetal growth restriction (FGR). Multigenerational Andean (AND) versus shorter duration European (EUR) high-altitude (HA) residents are protected from altitude-associated FGR. To address whether ancestry group differences in cytokine levels were involved, we conducted serial studies in 56 low-altitude ([LA]; 400 m; n=29 AND and n=27 EUR) and 42 HA residents (3600-4100 m; n=19 ANDs and n=23 EURs). Pregnancy raised pro-(interleukin 1 beta [IL-1 beta]) and anti-(IL-10) inflammatory cytokines and HA lowered IL-6 and tumor necrosis factor-alpha (TNF-alpha) near term. There were no ancestry group differences in cytokine levels at any time, but HA reduced IL-1 beta in ANDs only near term. Higher IL-1 beta levels correlated with uterine artery (UA) blood flow at 20 weeks in ANDs at HA, suggesting that IL-1 beta may play a role in AND protection from altitude-associated reductions in fetal growth.