Malaria elicits type 1 cytokines in the human placenta: IFN-gamma and TNF-alpha associated with pregnancy outcomes.

TLDR

Malaria infection during pregnancy, especially in primigravidas, is linked to maternal anemia and low birth weight, yet the mechanisms underlying poor fetal outcomes remain unclear because parasitemia is rarely detected in newborns. The study quantified cytokine concentrations in placentas from women delivering in urban Kenyan hospitals located in malaria‑holoendemic versus non‑endemic regions. Placental cytokine profiling revealed that malaria exposure shifts the balance toward type 1 cytokines—elevating IFN‑γ, IL‑2, and TNF‑α while reducing IL‑10—and that higher TNF‑α levels correlate with severe maternal anemia and low birth weight in primigravidas, linking these cytokine changes to adverse pregnancy outcomes.

Abstract

Pregnant women, especially primigravidas, are highly susceptible to malaria infection, resulting in maternal anemia and low birth weight infants. Because circulating parasitemia is rare in the newborn, the cause of poor fetal outcomes has been unclear. We measured cytokine concentrations in placentas collected from women delivering in urban hospitals in malaria-holoendemic or nonendemic areas of Kenya. Normal placentas displayed a bias toward type 2 cytokines; type 1 cytokines IFN-gamma and IL-2 were absent in placentas not exposed to malaria but present in a large proportion of placentas from a holoendemic area. TNF-alpha and TGF-beta concentrations were significantly higher, and IL-10 concentrations significantly lower, in placentas from the holoendemic area. Among primigravidas, placental TNF-alpha concentrations were significantly higher in the presence of severe maternal anemia, and both IFN-gamma and TNF-alpha were significantly elevated when a low birth weight, rather than normal weight, infant was delivered. We conclude that maternal malaria decreases IL-10 concentrations and elicits IFN-gamma, IL-2, and TNF-alpha in the placenta, shifting the balance toward type 1 cytokines. This is the first demonstration that these placental cytokine changes are associated with poor pregnancy outcomes in humans.