Immunity to Placental Malaria. I. Elevated Production of Interferon‐γ by Placental Blood Mononuclear Cells Is Associated with Protection in an Area with High Transmission of Malaria

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Abstract
In areas in which malaria is holoendemic, primigravidae and secundigravidae, compared with multigravidae, are highly susceptible to placental malaria (PM). The nature of gravidity-dependent immune protection against PM was investigated by measuring in vitro production of cytokines by placental intervillous blood mononuclear cells (IVBMC). The results demonstrated that interferon (IFN)-γ may be a critical factor in protection against PM: production of this cy tokine by PM-negative multigravid IVBMC was elevated compared with PM-negative primigravid and secundigravid and PM-positive multigravid cells. Low IFN-γ responsiveness to malarial antigen stimulation, most evident in the latter group, was balanced by increased interleukin (IL)-4 production, suggesting that counter-regulation of these two cytokines may be a crucial determinant in susceptibility to PM. A counter-regulatory relationship between IL-10 and tumor necrosis factor-α was also observed in response to malarial antigen stimulation. These data suggest that elevated production of IFN-γ, as part of a carefully regulated cytokine network, is important in the control of PM.

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