INFLAMMATORY CYTOKINE MESSENGER-RNAS IN SURGICAL SPECIMENS OF NECROTIZING ENTEROCOLITIS AND NORMAL NEWBORN INTESTINE

Coagulation necrosis, inflammation, and hemorrhage are pathologic hall marks of necrotizing enterocolitis (NEC). Because cytokines are peptid es that mediate inflammatory cell recruitment and amplify the immune r esponse, several of the inflammatory cytokines have been implicated in NEC. We hypothesized that mRNA levels for the interrelated cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha ), IL-6, and the neutrophil chemotactic factor IL-8 would be increased in NEC and would be associated with the presence of inflammation. In this study, we determined the relative levels and localization of mRNA for these cytokines in surgical pathology archival intestinal tissue from 29 premature infants with acute NEC and 15 control infants with c ongenital intestinal malformations using a novel quantitative in situ hybridization technique. Compared with controls, there were higher IL- 1 beta mRNA levels in full-thickness sections and higher TNF-alpha mRN A levels in full-thickness and mucosa sections of acute NEC samples, s uggesting a potential role for these cytokines in the pathogenesis of local inflammation in NEC. IL-6 and IL-8 mRNA levels were similar in s amples of control and acute NEC cases. Analysis of covariance includin g all subjects showed that the presence of acute inflammation was asso ciated with increased IL-1 beta mRNA levels in mucosa (P = .035) and i ncreased IL-8 in full-thickness sections (P = .005) and mucosa (P = .0 2). In four of five NEC cases in which intestinal specimens were avail able from reanastomosis surgery, cytokine mRNA levels decreased to low or undetectable levels. These data suggest that the inflammatory cyto kines are involved in neutrophil recruitment and augmentation of the i nflammatory response in neonatal intestine.