title: Increased circulating interleukin (IL)-23 in children with malarial anemia: in vivo and in vitro relationship with co-regulatory cytokines IL-12 and IL-10.
abstract: Severe malarial anemia (SMA) is a leading cause of mortality among children in sub-Saharan Africa. Although the novel cytokine, interleukin (IL)-23, promotes anemia in chronic inflammatory diseases, the role of IL-23 in SMA remains undefined. Since IL-23 and IL-12 share the IL-12p40 subunit and IL-12Rbeta1 receptor, and are down-regulated by IL-10, relationships among these cytokines were explored in Kenyan children with varying severities of malarial anemia. Children with malarial anemia had increased circulating IL-23 and IL-10 and decreased IL-12 relative to healthy controls. Enhanced anemia severity and elevated parasitemia were associated with increased IL-10 relative to IL-23 and IL-12. Further exploration of the relationships among the cytokines using an in vitro model in which peripheral blood mononuclear cells were treated with synthetic hemozoin (sHz, malarial pigment) revealed that IL-12p35 and IL-23p19 transcripts had a sustained induction over 72 h, while IL-12p40 and IL-10 message peaked at 24 h, and rapidly declined thereafter. Taken together, results here show that IL-23 is elevated in children with malarial anemia, and that IL-10 and IL-12 appear to have important regulatory effects on IL-23 production during childhood malaria.
authors.affiliation: University of Pittsburgh/KEMRI Laboratories of Parasitic and Viral Diseases, Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya. Jongecha@kisian.mimcom.net
authors.forename: John M
authors.initials: JM
authors.lastname: Ong'echa
authors.forename: Allison M
authors.initials: AM
authors.lastname: Remo
authors.forename: Jan
authors.initials: J
authors.lastname: Kristoff
authors.forename: James B
authors.initials: JB
authors.lastname: Hittner
authors.forename: Tom
authors.initials: T
authors.lastname: Were
authors.forename: Collins
authors.initials: C
authors.lastname: Ouma
authors.forename: Richard O
authors.initials: RO
authors.lastname: Otieno
authors.forename: John M
authors.initials: JM
authors.lastname: Vulule
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Keller
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Awandare
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Perkins
mesh_terms: D000740:Anemia / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D000818:Animals; D002675:Child, Preschool; D005260:Female; D006420:Hemeproteins / Q000276:immunology; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000097:blood* / Q000276:immunology; D018664:Interleukin-12 / Q000097:blood* / Q000276:immunology; D053759:Interleukin-23 / Q000097:blood* / Q000276:immunology; D007630:Kenya; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology; D008297:Male; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000276:immunology / Q000502:physiology; D021122:Protein Subunits / Q000276:immunology / Q000378:metabolism
chemical_list: D006420:Hemeproteins; D006454:Hemoglobins; D053759:Interleukin-23; D021122:Protein Subunits; D016753:Interleukin-10; D018664:Interleukin-12; C020753:hemozoin