Association between high cytokine levels with white matter injury in preterm infants with sepsis

Pediatr Crit Care Med. 2012 Mar;13(2):183-7. doi: 10.1097/PCC.0b013e3182231074.


Objective: To examine the association among interleukin-6, interleukin-8, tumor necrosis factor-α, interleukin-10, and interleukin-1β and white matter injury in very-low-birth-weight infants with clinical sepsis and to help predict infants at risk for development of white matter injury.

Design: A prospective cohort study was carried out.

Setting: Neonatal intensive care unit.

Patients: Very low birth weight infants with clinical early-onset sepsis. Exclusion criteria were death before 14 days, major malformations, and congenital infections.

Intervention: Ultrasound brain scans were carried out on the third day and weekly until the sixth week of life or discharge and confirmed by a magnetic resonance image performed in the first year. Plasma was assayed for interleukin-6, interleukin-8, tumor necrosis factor-α, interleukin-10, and interleukin-1β in the same sample collected for sepsis work-up. Mann-Whitney, chi-square, t tests, multiple regression, and receiver operating characteristic analysis were applied.

Measurements and main results: From July 2005 to October 2007 we studied 84 very-low-birth-weight infants, 27 (32%) with white matter injury, and 57 (68%) control subjects (with no white matter injury). Proven early-onset sepsis and necrotizing enterocolitis were high risk for white matter injury after adjustment for gestational age and birth weight (relative risk, 3.04; 1.93-4.80 and relative risk, 2.2; 1.31-3.74, respectively). Interleukin-6, interleukin-8, and tumor necrosis factor-α levels were higher in infants with white matter injury than in control subjects (p < .0001). Interleukin-1β and interleukin-10 were similar. The areas under the curve for interleukin-6, interleukin-8, and tumor necrosis factor-α were 0.96 (0.92-0.99), 0.97 (0.94-1.0), and 0.93 (0.86-0.99), respectively. Interleukin-8 ≥100 pg/mL was the best predictor of white matter injury; the sensitivity and specificity were 96% and 83%, respectively, and negative predictive value was 98%.

Conclusions: Very-low-birth-weight infants with proven early-onset sepsis, necrotizing enterocolitis, and high plasma levels of interleukin-6, interleukin-8, and tumor necrosis factor-α are at high risk for white matter injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Injuries / diagnostic imaging
  • Brain Injuries / epidemiology*
  • Cytokines / blood*
  • Female
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / blood*
  • Infant, Very Low Birth Weight*
  • Interleukin-10 / blood
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Interleukin-8 / blood
  • Leukoencephalopathies / diagnostic imaging
  • Leukoencephalopathies / epidemiology*
  • Male
  • Prospective Studies
  • Risk Factors
  • Sepsis / blood*
  • Tumor Necrosis Factor-alpha / blood
  • Ultrasonography


  • Cytokines
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Tumor Necrosis Factor-alpha
  • Interleukin-10