Intestinal cytokine gene expression in infants with acute necrotizing enterocolitis: interleukin-11 mRNA expression inversely correlates with extent of disease.
OBJECTIVE
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.
Nadler
E P
EP
Department of Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, PA 15213, USA.
Stanford
A
A
Zhang
X R
XR
Schall
L C
LC
Alber
S M
SM
Watkins
S C
SC
Ford
H R
HR
D000208:Acute Disease; D000704:Analysis of Variance; D046508:Culture Techniques; D016207:Cytokines / Q000032:analysis / Q000235:genetics*; D020345:Enterocolitis, Necrotizing / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers / Q000235:genetics; D006160:Guanosine Triphosphate / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D017370:Interleukin-11 / Q000235:genetics*; D018664:Interleukin-12 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D016015:Logistic Models; D008297:Male; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D016207:Cytokines; D005819:Genetic Markers; D017370:Interleukin-11; D016209:Interleukin-8; D012333:RNA, Messenger; D018664:Interleukin-12; D006160:Guanosine Triphosphate