PEDIATRICS Vol. 103 No. 4 April 1999, pp. 766-771
Circulating Pro- and Counterinflammatory Cytokine Levels and Severity in Necrotizing Enterocolitis
Received Feb 23, 1998; accepted Aug 27, 1998.
, and
From the * Division of Neonatal-Perinatal Medicine, Department
of Pediatrics, and the Division of Pediatric Surgery,
Department of Surgery, Medical College of Virginia of Virginia
Commonwealth University, Richmond, Virginia.
Objectives. To evaluate the
relationship between the severity of necrotizing enterocolitis (NEC)
and circulating concentrations of proinflammatory cytokines interleukin
(IL)-1
and IL-8 and counterinflammatory cytokines IL-1 receptor
antagonist (IL-1ra) and IL-10. These cytokines have been associated
with bowel injury or inflammation and may be released more slowly or
later than previously examined cytokines. Also, to determine if any one
of these cytokines will predict the eventual severity of NEC when
measured at symptom onset.
Method. Serial blood samples at onset, 8, 24, 48, and 72 hours were obtained from newborn infants with predefined signs and symptoms of NEC. Normal levels were defined from weight-, gestation-, and age-matched controls. Concentrations of the four cytokines were determined by enzyme-linked immunosorbent assay and compared throughout the time period by stage of NEC, using sepsis as a co-factor. Mean concentrations of each cytokine at onset were compared with the controls. Threshold values were obtained with the best combination of high sensitivity and high specificity for defining stage 1 NEC or for diagnosing stage 3 NEC at onset.
Results. There were 12 cases of stage 1, 18 cases of stage 2, and 6 cases of stage 3 NEC included in the study, as well as 20 control infants. Concentrations of IL-8 and IL-10 were significantly higher in infants with stage 3 NEC from onset through 24 hours compared with infants with less severe NEC. At onset, concentrations of all four cytokines were significantly higher in stage 3 NEC. To identify, at onset, the infants with a final diagnosis of stage 3 NEC, an IL-1ra concentration of >130 000 pg/mL had a sensitivity of 100% and a specificity of 92%. At 8 hours, an IL-10 concentration of >250 pg/mL had a sensitivity of 100% and a specificity of 90% in identifying stage 3 NEC in infants with symptoms suggestive of NEC at onset.
Conclusions. The severity of NEC and its systemic signs
and symptoms are not due to a deficiency of counterregulatory
cytokines. In fact, mean concentrations of IL-1ra in NEC are higher
than what has been reported in other populations. The cytokines IL-8,
IL-1ra, and IL-10 are released later or more slowly after a stimulus
and may be more useful in identifying, within hours of symptom onset, which infant will develop significant NEC.
Key words:
interleukin,
IL-1,
IL-8,
IL-10,
IL-1 receptor antagonist,
screening tests.
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