title: Elevated serum levels of IL-1ra in children with Plasmodium falciparum malaria are associated with increased severity of disease.
abstract: Animal models suggest that cytokines and chemokines play a role in cerebral malaria (CM) pathogenesis, but levels of a number of cytokines and chemokines thought to be important in the pathogenesis of other infectious diseases are not well characterized in children with CM. Serum levels of granulocyte-colony stimulating factor (G-CSF), interleukin-1 receptor antagonist (IL-1ra), interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were measured in 77 children with CM, 70 children with uncomplicated malaria (UM) and 63 healthy community children (CC) in Uganda. Children with CM had elevated serum levels of IL-1ra and IL-8 as compared to children with UM (median levels in pg/ml, 11,891 vs. 6510, P=0.05, and 63 vs. 41, P=0.01, respectively). Children with CM who died (n=4) had higher serum levels than survivors of IL-1ra (median levels in pg/ml, 65,757 vs. 10,355, P=0.02), G-CSF (709 vs. 117, P=0.02), and MCP-1 (1275 vs. 216, P=0.03) but not IL-8 (76 vs. 62, P=NS). Elevated IL-1ra levels are associated with increased disease severity in children with malaria, and very elevated levels of IL-1ra, G-CSF and MCP-1 are seen in children who die of CM.
authors.affiliation: Global Pediatrics Program and Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Minnesota Medical School, 420 Delaware Street, SE, 850 Mayo, MMC-296, Minneapolis, MN 55455, USA. ccj@umn.edu
authors.forename: Chandy C
authors.initials: CC
authors.lastname: John
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Park
authors.forename: Nadia
authors.initials: N
authors.lastname: Sam-Agudu
authors.forename: Robert O
authors.initials: RO
authors.lastname: Opoka
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Boivin
mesh_terms: D018925:Chemokines / Q000097:blood; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood* / Q000502:physiology; D016779:Malaria, Cerebral / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality*; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality*; D008297:Male; D012720:Severity of Illness Index; D014454:Uganda
chemical_list: D018925:Chemokines; D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein