Serum cytokines in a clinical trial of hypothermia for neonatal hypoxic-ischemic encephalopathy.
Inflammatory cytokines may mediate hypoxic-ischemic (HI) injury and offer insights into the severity of injury and the timing of recovery. In our randomized, multicenter trial of hypothermia, we analyzed the temporal relationship of serum cytokine levels in neonates with hypoxic-ischemic encephalopathy (HIE) with neurodevelopmental outcome at 12 months. Serum cytokines were measured every 12 hours for 4 days in 28 hypothermic (H) and 22 normothermic (N) neonates with HIE. Monocyte chemotactic protein-1 (MCP-1) and interleukins (IL)-6, IL-8, and IL-10 were significantly higher in the H group. Elevated IL-6 and MCP-1 within 9 hours after birth and low macrophage inflammatory protein 1a (MIP-1a) at 60 to 70 hours of age were associated with death or severely abnormal neurodevelopment at 12 months of age. However, IL-6, IL-8, and MCP-1 showed a biphasic pattern in the H group, with early and delayed peaks. In H neonates with better outcomes, uniform down modulation of IL-6, IL-8, and IL-10 from their peak levels at 24 hours to their nadir at 36 hours was observed. Modulation of serum cytokines after HI injury may be another mechanism of improved outcomes in neonates treated with induced hypothermia.
Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina 29425, USA. jenkd@musc.edu
Dorothea D
DD
Jenkins
Laura Grace
LG
Rollins
Jessica K
JK
Perkel
Carol L
CL
Wagner
Lakshmi P
LP
Katikaneni
W Thomas
WT
Bass
David A
DA
Kaufman
Michael J
MJ
Horgan
Sheela
S
Languani
Lawrence
L
Givelichian
Koravangattu
K
Sankaran
Jerome Y
JY
Yager
Renee H
RH
Martin
D001921:Brain / Q000098:blood supply; D018932:Chemokine CCL2 / Q000097:blood; D054405:Chemokine CCL3 / Q000097:blood; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000097:blood* / Q000175:diagnosis / Q000628:therapy*; D007223:Infant; D007231:Infant, Newborn; D018664:Interleukin-12 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D011379:Prognosis; D012737:Sex Factors; D013997:Time Factors; D016896:Treatment Outcome
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D016207:Cytokines; D015850:Interleukin-6; D018664:Interleukin-12