Cytokine elevations in critically ill infants with sepsis and necrotizing enterocolitis,☆☆,

https://doi.org/10.1016/S0022-3476(94)70264-0Get rights and content

Abstract

We hypothesized that plasma levels of cytokines such as interleukin-6 and tumor necrosis factor (TNF) are elevated in critically ill infants with sepsis and necrotizing enterocolitis (NEC) and that the magnitude of their elevation is correlated with mortality rate. We measured plasma levels of interleukin-6 and TNF in 62 newborn infants with suspected sepsis or NEC. Eighteen infants had bacterial sepsis, 9 had bacterial sepsis plus NEC, and 15 had NEC but negative culture results. Twenty comparably ill infants with negative results on culture of systemic specimens served as study control subjects. Interleukin-6 levels were five- to tenfold higher in infants with bacterial sepsis plus NEC at the onset of disease than in infants with bacterial sepsis alone, in infants with NEC but negative culture results, and in control infants (p <0.01). These differences persisted throughout the 48-hour study period. Interleukin-6 levels were also significantly higher in nonsurvivors than in survivors (p <0.001). In contrast, plasma TNF values were not consistently increased in any of the groups. We conclude that plasma interleukin-6 is a more reliable indicator of bacterial sepsis and NEC than plasma TNF and may identify infants who might benefit from immunotherapeutic strategies. (J PEDIATR 1994;124:105-11)

Section snippets

Study population

All neonates with suspected sepsis who were hospitalized in the infant intensive care unit of Children's Hospital of Philadelphia during the 36-month period beginning in April 1989 were eligible for enrollment in the study. Inclusion criteria included all of the following: (1) a risk factor for infection, (2) physical examination demonstrating either respiratory or circulatory dysfunction, and (3) physical signs of infection.

A risk factor for infection included at least one of the following:

Study population

Sixty-two infants with suspected sepsis who met inclusion criteria were enrolled. These infants had a birth weight of 1.6 ± 0.95 kg (mean ± SD) and a mean gestational age of 30 weeks (range 22 to 41 weeks). Among the entire group of study infants 73% were premature, 58% had been hospitalized >7 days, and 81% had a foreign body in place (endotracheal tube, chest tube, or ventriculoperitoneal shunt, including 10% with central intravascular catheters) at the time of enrollment. Ninety-eight

DISCUSSION

Previous studies in adults have implicated the cytokines TNF, IL-1, and IL-6 as important endogenous mediators in the pathogenesis of sepsis and shock.6, 7, 8, 9 Several studies have demonstrated elevated TNF levels in adults with bacterial sepsis, which correlated with mortality rates.6, 7 Similarly, Waage et al.9 and Hack et al.10 demonstrated increased levels of IL-6 in the plasma of adults with bacterial sepsis, and these were associated with an increased incidence of shock and death.

Data

References (25)

  • A Waage et al.

    Interleukin-1 potentiates the lethal effect of tumor necrosis factor α/cachectin in mice

    J Exp Med

    (1988)
  • JG Cannon et al.

    Interleukin-1β in human plasma: optimization of blood collection, plasma extraction, and radioimmunoassay methods

    Lymphokine Res

    (1988)
  • Cited by (188)

    • Genetic Basis of Necrotizing Enterocolitis

      2018, Hematology, Immunology and Genetics: Neonatology Questions and Controversies
    View all citing articles on Scopus

    From the Division of Neonatology, the Division of Allergy, Immunology and Infectious Diseases, the Department of Pediatrics, and the Department of Anesthesia and Critical Care Medicine, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia

    ☆☆

    Reprint requests: Mary Catherine Harris, MD, Division of Neonatology, Children's Hospital of Philadelphia, 34th Street and Civic Center Blvd., Philadelphia, PA 19104.

    0022-3476/94/$1.00 + .10 9/23/50952

    View full text