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

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 (MgSO4) 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 MgSO4, 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 MgSO4 was efficacious in aborting the activation of TNF-α but did not alter the expression of IL-1β or IL-6. © 2011 - IOS Press and the authors. All rights reserved.