Intestinal cytokine gene expression in infants with acute necrotizing enterocolitis: Interleukin-11 mRNA expression inversely correlates with extent of disease

Background/Purpose: The authors have shown previously that surgical specime ns from infants with acute necrotizing enterocolitis (NEC) show upregulatio n of inducible nitric oxide (NO) synthase (iNOS) and interferon-gamma mRNA. However, the contribution of other inflammatory cytokines such as interleu kin-8 (IL-8), IL-11, and IL-12 has not been defined. Likewise, the role of GTP-cyclohydrolase, the rate-limiting enzyme in tetrahydrobiopterin synthes is, and thus NO production by iNOS is unclear. In this study, the authors s ought to further define the pattern of cytokine expression seen in infants with acute NEC. Methods: The authors measured intestinal cytokine mRNA expression by semiqu antitative reverse transcriptase polymerase chain reaction in 21 infants wi th histologically confirmed NEC, 18 with other inflammatory conditions, and in 9 patients without intestinal inflammation. Guanosine triphosphate-cycl ohydrolase (GTP-CH) activity was measured by specific enzyme assay. Univari ate exact logistic regression analysis was performed to identify predictors of outcome. Results: IL-8 and IL-11 mRNA were upregulated in patients with acute NEC co mpared with those with other inflammatory conditions or those without disea se; these levels returned to baseline at the time of stoma closure. Increas ed IL-11 mRNA decreased the likelihood of pan-necrosis (odds ratio, 0.93; P =.002). Increased IL-12 levels (but not IL-8) seemed to protect against pa n-necrosis (odds ratio, 0.70; P=.06). Conclusions: Local upregulation of IL-11 may represent an adaptive response designed to limit the extent of intestinal damage in NEC. Decreased IL-12 levels may contribute to the pathogenesis of NEC by allowing bacteria to es cape host defenses. J Pediatr Surg 36:1122-1129. Copyright (C) 2001 by W.B. Saunders Company.