title: Cytokine profiles at birth predict malaria severity during infancy.
abstract: BACKGROUND
  Severe malaria risk varies between individuals, and most of this variation remains unexplained. Here, we examined the hypothesis that cytokine profiles at birth reflect inter-individual differences that persist and influence malaria parasite density and disease severity throughout early childhood.
  
  
  RESULTS
  Cytokine levels (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6 and IL-10) were measured at birth (cord blood; N=783) and during subsequent routine follow-up visits (peripheral blood) for children enrolled between 2002 and 2006 into a birth cohort in Muheza, Tanzania. Children underwent blood smear and clinical assessments every 2-4 weeks, and at the time of any illness. Cord blood levels of all cytokines were positively correlated with each other (Spearman's rank correlation). Cord levels of IL-1β and TNF-α (but not other cytokines) correlated with levels of the same cytokine measured at routine visits during early life (P < 0.05). Higher cord levels of IL-1β but not TNF-α were associated with lower parasite densities during infancy (P=0.003; Generalized Estimating Equation (GEE) method), with an average ~40% reduction versus children with low cord IL-1β levels, and with decreased risk of severe malaria during follow-up (Cox regression): adjusted hazard ratio (95% CI) 0.60 (0.39-0.92), P = 0.02.
  
  
  CONCLUSIONS
  IL-1β levels at birth are related to future IL-1β levels as well as the risk of severe malaria in early life. The effect on severe malaria risk may be due in part to the effect of inflammatory cytokines to control parasite density.
authors.affiliation: MOMS Project, Seattle Biomedical Research Institute, Seattle, Washington, United States of America, and Muheza Designated District Hospital, Muheza, Tanzania.
authors.forename: Edward
authors.initials: E
authors.lastname: Kabyemela
authors.forename: Bronner P
authors.initials: BP
authors.lastname: Gonçalves
authors.forename: D Rebecca
authors.initials: DR
authors.lastname: Prevots
authors.forename: Robert
authors.initials: R
authors.lastname: Morrison
authors.forename: Whitney
authors.initials: W
authors.lastname: Harrington
authors.forename: Moses
authors.initials: M
authors.lastname: Gwamaka
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Kurtis
authors.forename: Michal
authors.initials: M
authors.lastname: Fried
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Duffy
mesh_terms: D002675:Child, Preschool; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D006801:Humans; D007223:Infant; D008288:Malaria / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology / Q000469:parasitology; D008297:Male; D036801:Parturition / Q000097:blood*; D010961:Plasmodium / Q000502:physiology; D012306:Risk; D012720:Severity of Illness Index; D013636:Tanzania / Q000453:epidemiology
chemical_list: D016207:Cytokines