title: Decreased circulating macrophage migration inhibitory factor (MIF) protein and blood mononuclear cell MIF transcripts in children with Plasmodium falciparum malaria.
abstract: Plasmodium falciparum malaria remains one of the most frequently lethal diseases affecting children in sub-Saharan Africa, yet the immune mediators that regulate pathogenesis are only partially defined. Since macrophage migration inhibitory factor (MIF) is important for regulating innate immunity in bacterial and parasitic infections, circulating MIF and peripheral blood mononuclear cell (PBMC) MIF transcripts were investigated in children with acute falciparum malaria. Peripheral blood levels of MIF-regulatory cytokines and effector molecules, including interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-12, IL-10, transforming growth factor (TGF)-beta1, bicyclo-prostaglandin (PG) E2, and nitric oxide synthase activity were also determined. Circulating MIF and PBMC MIF mRNA were significantly lower in children with acute malaria relative to healthy, malaria-exposed children. Peripheral blood MIF levels showed no association with either parasitemia or hemoglobin concentrations. Circulating MIF was, however, significantly associated with IL-12 and TGF-beta1. Multiple regression analyses revealed that IFN-gamma was the most significant predictor of peripheral blood MIF concentrations. These findings suggest that reduced MIF production may promote enhanced disease severity in children with falciparum malaria.
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, 603 Parran Hall, Pittsburgh, PA 15261, USA.
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Awandare
authors.forename: James B
authors.initials: JB
authors.lastname: Hittner
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Ochiel
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Keller
authors.forename: J Brice
authors.initials: JB
authors.lastname: Weinberg
authors.forename: Ian A
authors.initials: IA
authors.lastname: Clark
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Perkins
mesh_terms: D000818:Animals; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D016778:Malaria, Falciparum / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood; D012720:Severity of Illness Index; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: D016207:Cytokines; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger