title: Altered circulating leukocytes and their chemokines in a clinical trial of therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy*.
abstract: OBJECTIVE
  To determine systemic hypothermia's effect on circulating immune cells and their corresponding chemokines after hypoxic ischemic encephalopathy in neonates.
  
  
  METHODS
  In our randomized, controlled, multicenter trial of systemic hypothermia in neonatal hypoxic ischemic encephalopathy, we measured total and leukocyte subset and serum chemokine levels over time in both hypothermia and normothermia groups, as primary outcomes for safety.
  
  
  METHODS
  Neonatal ICUs participating in a Neurological Disorders and Stroke sponsored clinical trial of therapeutic hypothermia.
  
  
  METHODS
  Sixty-five neonates with moderate to severe hypoxic ischemic encephalopathy within 6 hours after birth.
  
  
  METHODS
  Patients were randomized to normothermia of 37°C or systemic hypothermia of 33°C for 48 hours.
  
  
  RESULTS
  Complete and differential leukocyte counts and serum chemokines were measured every 12 hours for 72 hours. The hypothermia group had significantly lower median circulating total WBC and leukocyte subclasses than the normothermia group before rewarming, with a nadir at 36 hours. Only the absolute neutrophil count rebounded after rewarming in the hypothermia group. Chemokines, monocyte chemotactic protein-1 and interleukin-8, which mediate leukocyte chemotaxis as well as bone marrow suppression, were negatively correlated with their target leukocytes in the hypothermia group, suggesting active chemokine and leukocyte modulation by hypothermia. Relative leukopenia at 60-72 hours correlated with an adverse outcome in the hypothermia group.
  
  
  CONCLUSIONS
  Our data are consistent with chemokine-associated systemic immunosuppression with hypothermia treatment. In hypothermic neonates, persistence of lower leukocyte counts after rewarming is observed in infants with more severe CNS injury.
authors.affiliation: 1Department of Pediatrics, Medical University of South Carolina, Charleston, SC. 2Department of Pediatric Emergency Medicine, Akron Children's Hospital, Akron, OH. 3Department of Medicine, Division of Biostatistics and Epidemiology, Medical University of South Carolina, Charleston, SC. 4Department of Clinical Psychology, University of Massachusetts, Boston, MA. 5Department of Pediatrics, Eastern Virginia Medical School, Norfolk, VA. 6Department of Pediatrics, University of Virginia, Charlottesville, VA. 7Department of Pediatrics, Albany Medical Center, Albany, NY. 8Department of Pediatrics, Brooklyn Hospital Center, Brooklyn, NY. 9Department of Pediatrics, University of Saskatchewan, Saskatoon, SK, Canada. 10Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
authors.forename: Dorothea D
authors.initials: DD
authors.lastname: Jenkins
authors.forename: Timothy
authors.initials: T
authors.lastname: Lee
authors.forename: Cody
authors.initials: C
authors.lastname: Chiuzan
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Perkel
authors.forename: Laura Grace
authors.initials: LG
authors.lastname: Rollins
authors.forename: Carol L
authors.initials: CL
authors.lastname: Wagner
authors.forename: Lakshmi P
authors.initials: LP
authors.lastname: Katikaneni
authors.forename: W Thomas
authors.initials: WT
authors.lastname: Bass
authors.forename: David A
authors.initials: DA
authors.lastname: Kaufman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Horgan
authors.forename: Sheela
authors.initials: S
authors.lastname: Laungani
authors.forename: Laurence M
authors.initials: LM
authors.lastname: Givelichian
authors.forename: Koravangatta
authors.initials: K
authors.lastname: Sankaran
authors.forename: Jerome Y
authors.initials: JY
authors.lastname: Yager
authors.forename: Renee
authors.initials: R
authors.lastname: Martin
mesh_terms: D018925:Chemokines / Q000097:blood*; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000097:blood* / Q000628:therapy*; D007223:Infant; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018925:Chemokines