title: Early cytokine induction by Plasmodium falciparum is not a classical endotoxin-like process.
abstract: We have investigated the widely held view that malaria parasites induce pro-inflammatory cytokines primarily through an endotoxin-like stimulatory effect on macrophages. We report that the pattern of cytokine production by non-immune human peripheral blood mononuclear cells following stimulation by Plasmodium falciparum-infected erythrocytes (Pfe) in vitro differs considerably from that induced by bacterial endotoxin. The Pfe-induced TNF response at day 1 is associated with a much higher level of IFN-gamma production and a much lower level of IL-12 p40 and IL-10 expression than a comparable endotoxin-induced TNF response. Both CD3(+) and CD14(+) populations are required for this early TNF response to Pfe, whereas the endotoxin-induced response is unaffected by depletion of the CD3(+) population. Pfe fails to stimulate the monocyte-like cell line MonoMac6 to express pro-inflammatory cytokines. These findings suggest that the early inflammatory response to malaria is critically dependent on lymphocyte subpopulations that play a lesser role in the response to bacterial endotoxin.
authors.affiliation: Oxford University Department of Paediatrics, John Radcliffe Hospital, Oxford, GB.
authors.forename: I G
authors.initials: IG
authors.lastname: Scragg
authors.forename: M
authors.initials: M
authors.lastname: Hensmann
authors.forename: C A
authors.initials: CA
authors.lastname: Bate
authors.forename: D
authors.initials: D
authors.lastname: Kwiatkowski
mesh_terms: D000818:Animals; D001483:Base Sequence; D017252:CD3 Complex / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000469:parasitology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D010963:Plasmodium falciparum / Q000276:immunology* / Q000472:pathogenicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D017252:CD3 Complex; D016207:Cytokines; D017931:DNA Primers; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha