Faculty Collaboration Database

Intestinal cytokine gene expression in infants with acute necrotizing enterocolitis: interleukin-11 mRNA expression inversely correlates with extent of disease. J Pediatr Surg 2001 Aug;36(8):1122-9

Date

08/02/2001

Pubmed ID

11479840

DOI

10.1053/jpsu.2001.25726

Scopus ID

2-s2.0-0034909471 (requires institutional sign-in at Scopus site)   75 Citations

Abstract

BACKGROUND/PURPOSE: The authors have shown previously that surgical specimens from infants with acute necrotizing enterocolitis (NEC) show upregulation of inducible nitric oxide (NO) synthase (iNOS) and interferon-gamma mRNA. However, the contribution of other inflammatory cytokines such as interleukin-8 (IL-8), IL-11, and IL-12 has not been defined. Likewise, the role of GTP-cyclohydrolase, the rate-limiting enzyme in tetrahydrobiopterin synthesis, and thus NO production by iNOS is unclear. In this study, the authors sought to further define the pattern of cytokine expression seen in infants with acute NEC.

METHODS: The authors measured intestinal cytokine mRNA expression by semiquantitative reverse transcriptase polymerase chain reaction in 21 infants with histologically confirmed NEC, 18 with other inflammatory conditions, and in 9 patients without intestinal inflammation. Guanosine triphosphate-cyclohydrolase (GTP-CH) activity was measured by specific enzyme assay. Univariate 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 compared with those with other inflammatory conditions or those without disease; these levels returned to baseline at the time of stoma closure. Increased 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 pan-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 escape host defenses.

Author List

Nadler EP, Stanford A, Zhang XR, Schall LC, Alber SM, Watkins SC, Ford HR

Author

Laura Cassidy PhD Associate Dean, Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Disease
Analysis of Variance
Culture Techniques
Cytokines
Enterocolitis, Necrotizing
Female
Gene Expression Regulation
Genetic Markers
Guanosine Triphosphate
Humans
Immunohistochemistry
Infant
Infant, Newborn
Interleukin-11
Interleukin-12
Interleukin-8
Logistic Models
Male
Prognosis
RNA, Messenger
Reference Values
Reverse Transcriptase Polymerase Chain Reaction
Sensitivity and Specificity
Severity of Illness Index