Malaria Elicits Type 1 Cytokines in the Human Placenta: IFN-γ and TNF-α Associated with Pregnancy Outcomes

TLDR

Pregnant women, especially primigravidas, are highly susceptible to malaria, which is linked to maternal anemia and low‑birth‑weight infants, yet the mechanism behind poor fetal outcomes remains unclear because newborns rarely show circulating parasitemia. The study quantified cytokine levels in placentas from women delivering in Kenyan urban hospitals, comparing samples from malaria‑holoendemic and nonendemic regions. Malaria exposure shifted placental cytokine balance toward type‑1 cytokines—elevating IFN‑γ, IL‑2, and TNF‑α while reducing IL‑10—and higher TNF‑α correlated with severe maternal anemia and low‑birth‑weight infants, demonstrating that these cytokine changes associate with adverse pregnancy outcomes.

Abstract

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-γ and IL-2 were absent in placentas not exposed to malaria but present in a large proportion of placentas from a holoendemic area. TNF-α and TGF-β concentrations were significantly higher, and IL-10 concentrations significantly lower, in placentas from the holoendemic area. Among primigravidas, placental TNF-α concentrations were significantly higher in the presence of severe maternal anemia, and both IFN-γ and TNF-α 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-γ, IL-2, and TNF-α 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.