Immunity to placental malaria. I. Elevated production of interferon-gamma by placental blood mononuclear cells is associated with protection in an area with high transmission of malaria

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 in vestigated by measuring in vitro production of cytokines by placental inter villous blood mononuclear cells (IVBMC). The results demonstrated that inte rferon (IFN)-gamma may be a critical factor in protection against PM: produ ction of this cytokine by PM-negative multigravid IVBMC was elevated compar ed with PM-negative primigravid and secundigravid and PM-positive multigrav id cells. Low IFN-gamma responsiveness to malarial antigen stimulation, mos t 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 rela tionship between IL-IO and tumor necrosis factor-alpha was also observed in response to malarial antigen stimulation. These data suggest that elevated production of IFN-gamma, as part of a carefully regulated cytokine network , is important in the control of PM.