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.
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.
Ong'echa
John M
JM
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
Remo
Allison M
AM
Kristoff
Jan
J
Hittner
James B
JB
Were
Tom
T
Ouma
Collins
C
Otieno
Richard O
RO
Vulule
John M
JM
Keller
Christopher C
CC
Awandare
Gordon A
GA
Perkins
Douglas J
DJ
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
D006420:Hemeproteins; D006454:Hemoglobins; D053759:Interleukin-23; D021122:Protein Subunits; D016753:Interleukin-10; D018664:Interleukin-12; C020753:hemozoin