MALARIA ELICITS TYPE-1 CYTOKINES IN THE HUMAN PLACENTA - IFN-GAMMA AND TNF-ALPHA ASSOCIATED WITH PREGNANCY OUTCOMES

Pregnant women, especially primigravidas, are highly susceptible to ma laria infection, resulting in maternal anemia and low birth weight inf ants, Because circulating parasitemia is rare in the newborn, the caus e of poor fetal outcomes has been unclear, We measured cytokine concen trations in placentas collected from women delivering in urban hospita ls in malaria-holoendemic or nonendemic areas of Kenya. Normal placent as displayed a bias toward type 2 cytokines; type 1 cytokines IFN-gamm a 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 conc entrations significantly lower, in placentas from the holoendemic area , Among primigravidas, placental TNF-alpha concentrations were signifi cantly higher in the presence of severe maternal anemia, and both IFN- gamma and TNF-alpha were significantly elevated when a low birth weigh t, rather than normal weight, infant was delivered, We conclude that m aternal 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 cyto kine changes are associated with poor pregnancy outcomes in humans.