肿瘤坏死因子α
免疫学
血凝蛋白
寄生虫血症
外周血单个核细胞
发病机制
疟疾
恶性疟原虫
生物
前列腺素E2
医学
内分泌学
生物化学
体外
作者
Christopher C. Keller,Gregory C. Davenport,Katherine R. Dickman,James B. Hittner,Sandra S. Kaplan,J. Brice Weinberg,Peter G. Kremsner,Douglas J Perkins
摘要
Cytokines and effector molecules are important immunoregulatory molecules in human malaria. Tumor necrosis factor (TNF)–α limits malaria parasitemia but also promotes pathogenesis at high concentrations, whereas prostaglandin E2 (PGE2) inhibits TNF-α production and is reduced in childhood malaria, at least in part, through suppression of cyclooxygenase (COX)–2 following the ingestion of Plasmodium falciparum hemozoin (pfHz; malarial pigment) by peripheral blood mononuclear cells (PBMCs). Although molecular interactions between TNF-α and PGE2 are largely unexplored in human malaria, results presented here show that pfHz-induced suppression of PBMC COX-2 gene products induces overproduction of TNF-α. Moreover, addition of exogenous PGE2 to pfHz-treated PBMCs dose-dependently decreased TNF-α production, whereas experimental COX inhibitors and antipyretics used during human malaria generated increased TNF-α production. Healthy, malaria-exposed children had elevated levels of circulating bicyclo-PGE2/TNF-α, compared with children with malarial anemia (P<.01), with systemic bicyclo-PGE2 and TNF-α significantly associated with hemoglobin concentrations (r=0.745; P<.01). The results of the present study illustrate that pfHz-induced suppression of PGE2 promotes overproduction of TNF-α, which is associated with enhanced malarial anemia
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