Circulating pro- and counterinflammatory cytokine levels and severity in necrotizing enterocolitis

Objectives. To evaluate the relationship between the severity of necrotizin g enterocolitis (NEC) and circulating concentrations of proinflammatory cyt okines interleukin (IL)-1 beta and IL-8 and counterinflammatory cytokines I L-1 receptor antagonist (IL-1ra) and IL-10. These cytokines have been assoc iated 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 obtaine d from newborn infants with predefined signs and symptoms of NEC. Normal le vels were defined from weight-, gestation-, and age-matched controls. Conce ntrations of the four cytokines were determined by enzyme-linked immunosorb ent assay and compared throughout the time period by stage of NEC, using se psis as a co-factor. Mean concentrations of each cytokine at onset were com pared with the controls. Threshold values were obtained with the best combi nation 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 o f stage 3 NEC included in the study, as well as 20 control infants. Concent rations 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 o f 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 >25 0 pg/mL had a sensitivity of 100% and a specificity of 90% in identifying s tage 3 NEC in infants with symptoms suggestive of NEC at onset. Conclusions. The severity of NEC and its systemic signs and symptoms are no t due to a deficiency of counterregulatory cytokines. In fact, mean concent rations of IL-1ra in NEC are higher than what has been reported in other po pulations. 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 hour s of symptom onset, which infant will develop significant NEC.