In areas of high malaria endemicity, women have increased susceptibility to malaria during pregnancy characterized by placental parasitemia. Our previous studies in children with malaria demonstrate that suppression of leukocyte-derived prostaglandin-E-2 (PGE(2)) is associated with enhanced pathogenesis. To examine the role of PGE(2) as an immunoregulatory molecule in placental malaria, PGE(2) was determined in cultured intervillous blood mononuclear cells (IVBMCs) from aparasitemic and parasitemic women. PGE(2) was significantly lower in parasitemic women at all gravidities. Women with a positive antenatal peripheral parasitemia who were negative for placental malaria (PM) at term produced the highest PGE(2) levels. Suppression of PGE(2) was associated with increasing amounts of hemozoin (malarial pigment) acquired during the natural infection. PGE(2) regulatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)-10, were non-significantly increased in IVBMC containing an intermediate amount of hemozoin and significantly suppressed in IVBMC with high levels of hemozoin. Results presented here show that in vivo acquisition of high levels of hemozoin by IVBMC leads to decreased synthesis of PGE(2), IL-10, and TNF-alpha. (C) 2003 Elsevier Inc. All rights reserved.