Interleukin-1β, interleukin-6, and tumor
necrosis factor-α in the cerebrospinal fluid of term
infants with hypoxic-ischemic encephalopathy after postnatal treatment with magnesium sulfate
Affiliations: Department of Pediatrics, Mansoura University
Children's Hospital, Mansoura, Egypt | Department of Gastroenterology, Mansoura University,
Mansoura, Egypt | Department of Newborn Services, The George Washington
University and the Children's National Medical Center, Washington, DC,
USA
Note: [] Correspondence: Dr. Hany Aly, M.D., FAAP, 900 23rd Street, NW,
Suite G2092, 20037, Washington, DC, USA. Tel.: +1 202 715 5350; Fax: +1 202
715 5354; E-mail: haly@mfa.gwu.edu
Abstract: Proinflammatory cytokines play a role in the pathogenesis of
hypoxic-ischemic encephalopathy (HIE). We aimed: 1) to characterize the
expression of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α
(TNF-α) in the cerebrospinal fluid (CSF) of term
infants with HIE, and 2) to determine the impact of a single dose of magnesium
sulfate (MgSO_{4}) on their concentrations. We analyzed the
samples of CSF that were collected during a randomized controlled trial on the
use of MgSO_{4} in neonatal asphyxia. Two samples were
obtained from each subject; one was obtained on admission and the second sample
was collected at 72 hr of life. The grades of HIE in the 47 included newborns
were mild (n=15), moderate (n=17), and
severe (n=15). After the collection of the first CSF
sample, 23 newborns received a single dose of MgSO_{4},
whereas the other 24~newborns received an equal volume of normal saline
placebo. Concentrations of IL-1β, IL-6 and
TNF-α in the CSF were quantified by enzyme-linked
immunosorbent assay in all CSF samples. The initial concentration of
IL-1β and IL-6 correlated with the severity grades of
HIE (P= 004 and P=0001, respectively)
while TNF-α did not. At 72 hr, a significant decline
in the concentration of TNF-α (pg/mL) was observed in
samples of MgSO_{4}-treated infants when compared to the
control group (-28 ± 90 vs. 102
± 404, P=0.01), whereas the two
treatment groups did not differ in IL-1β or IL-6.
Short-term clinical outcomes correlated best with IL-1β
at baseline, IL-6 at baseline and IL-6 at 72 hr. We conclude that cytokine
activation, as manifested by increased IL-1β and IL-6
in the CSF, is positively correlated with the severity of HIE. Treatment with a
single dose of MgSO_{4} was efficacious in aborting the
activation of TNF-α but did not alter the expression
of IL-1β or IL-6.
