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

Evan P. Nadler, Ala Stanford, Xiao Ru Zhang, Laura C. Schall, Sean M. Alber, Simon C. Watkins, Henri Ford

Research output: Contribution to journalArticle

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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-γ 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.

Original languageEnglish (US)
Pages (from-to)1122-1129
Number of pages8
JournalJournal of Pediatric Surgery
Volume36
Issue number8
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Fingerprint

Interleukin-11
Necrotizing Enterocolitis
Cytokines
Gene Expression
Messenger RNA
Interleukin-12
Interleukin-8
Necrosis
Up-Regulation
GTP Cyclohydrolase
Odds Ratio
Enzyme Assays
Nitric Oxide Synthase Type II
Guanosine Triphosphate
Reverse Transcriptase Polymerase Chain Reaction
Interferons
Nitric Oxide
Logistic Models
Regression Analysis
Inflammation

Keywords

  • Cytokines
  • Gene expression
  • Guanosine triphosphate-cyclohydrolase
  • Interleukin-11
  • Interleukin-12
  • Interleukin-8
  • Necrotizing enterocolitis

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

Cite this

Intestinal cytokine gene expression in infants with acute necrotizing enterocolitis : Interleukin-11 mRNA expression inversely correlates with extent of disease. / Nadler, Evan P.; Stanford, Ala; Zhang, Xiao Ru; Schall, Laura C.; Alber, Sean M.; Watkins, Simon C.; Ford, Henri.

In: Journal of Pediatric Surgery, Vol. 36, No. 8, 01.01.2001, p. 1122-1129.

Research output: Contribution to journalArticle

Nadler, Evan P. ; Stanford, Ala ; Zhang, Xiao Ru ; Schall, Laura C. ; Alber, Sean M. ; Watkins, Simon C. ; Ford, Henri. / Intestinal cytokine gene expression in infants with acute necrotizing enterocolitis : Interleukin-11 mRNA expression inversely correlates with extent of disease. In: Journal of Pediatric Surgery. 2001 ; Vol. 36, No. 8. pp. 1122-1129.
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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-γ 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.",
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T1 - Intestinal cytokine gene expression in infants with acute necrotizing enterocolitis

T2 - Interleukin-11 mRNA expression inversely correlates with extent of disease

AU - Nadler, Evan P.

AU - Stanford, Ala

AU - Zhang, Xiao Ru

AU - Schall, Laura C.

AU - Alber, Sean M.

AU - Watkins, Simon C.

AU - Ford, Henri

PY - 2001/1/1

Y1 - 2001/1/1

N2 - 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-γ 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.

AB - 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-γ 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.

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KW - Gene expression

KW - Guanosine triphosphate-cyclohydrolase

KW - Interleukin-11

KW - Interleukin-12

KW - Interleukin-8

KW - Necrotizing enterocolitis

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