title: Cytokines associated with necrotizing enterocolitis in extremely-low-birth-weight infants.
abstract: BACKGROUND
  The goal was to identify cytokines associated with necrotizing enterocolitis (NEC). Based on our earlier reports of decreased tissue expression of transforming growth factor (TGF)-β, we hypothesized that infants with NEC also have low blood TGF-β levels. We further hypothesized that because fetal inflammation increases the risk of NEC, infants who develop NEC have elevated blood cytokine levels in early neonatal period.
  
  
  METHODS
  Data on 104 extremely-low-birth-weight infants with NEC and 893 without NEC from 17 centers were analyzed. Clinical information was correlated with blood cytokine levels on postnatal day 1 (D1), D3, D7, D14, and D21.
  
  
  RESULTS
  Male gender, non-Caucasian/non-African American ethnicity, sepsis, lower blood TGF-β and interleukin (IL)-2 levels, and higher IL-8 levels were associated with NEC. The NEC group had lower TGF-β levels than controls since D1. The diagnosis of NEC was associated with elevated IL-1β, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1/CC-motif ligand-2, macrophage inflammatory protein-1β/CC-motif ligand-3, and C-reactive protein.
  
  
  CONCLUSIONS
  Clinical characteristics, such as gender and ethnicity, and low blood TGF-β levels are associated with higher risk of NEC. Infants who developed NEC did not start with high blood levels of inflammatory cytokines, but these rose mainly after the onset of NEC.
authors.affiliation: 1] Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama [2] Department of Pediatrics, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Akhil
authors.initials: A
authors.lastname: Maheshwari
authors.affiliation: 1] Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama [2] Department of Pediatrics, Oregon Health and Science University, Portland, Oregon.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Schelonka
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Reed A
authors.initials: RA
authors.lastname: Dimmitt
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Waldemar A
authors.initials: WA
authors.lastname: Carlo
authors.affiliation: Statistics and Epidemiology Unit, RTI International, Research Triangle Park, North Carolina.
authors.forename: Breda
authors.initials: B
authors.lastname: Munoz-Hernandez
authors.affiliation: Statistics and Epidemiology Unit, RTI International, Research Triangle Park, North Carolina.
authors.forename: Abhik
authors.initials: A
authors.lastname: Das
authors.affiliation: Statistics and Epidemiology Unit, RTI International, Research Triangle Park, North Carolina.
authors.forename: Scott A
authors.initials: SA
authors.lastname: McDonald
authors.affiliation: Department of Obstetrics and Gynecology, Lillebaelt Hospital, Kolding, Denmark.
authors.forename: Poul
authors.initials: P
authors.lastname: Thorsen
authors.affiliation: Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Kristin
authors.initials: K
authors.lastname: Skogstrand
authors.affiliation: Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: David M
authors.initials: DM
authors.lastname: Hougaard
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: Rosemary D
authors.initials: RD
authors.lastname: Higgins
mesh_terms: D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood*; D020345:Enterocolitis, Necrotizing / Q000097:blood*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D052577:Infant, Extremely Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D007249:Inflammation / Q000097:blood*; D007376:Interleukin-2 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D015203:Reproducibility of Results; D012306:Risk; D016212:Transforming Growth Factor beta / Q000097:blood
chemical_list: D015415:Biomarkers; C508606:CXCL8 protein, human; D016207:Cytokines; C508594:IL2 protein, human; D007376:Interleukin-2; D016209:Interleukin-8; D016212:Transforming Growth Factor beta
references.citation: Pediatr Res. 2003 Aug;54(2):160-4
references.pmid: 12736398
references.citation: Am J Physiol Gastrointest Liver Physiol. 2013 Jan 15;304(2):G167-80
references.pmid: 23154975
references.citation: Curr Opin Immunol. 2007 Feb;19(1):55-62
references.pmid: 17137775
references.citation: Proc Natl Acad Sci U S A. 2000 May 23;97(11):6043-8
references.pmid: 10823949
references.citation: Pediatr Dev Pathol. 1998 Jan-Feb;1(1):2-16
references.pmid: 10463267
references.citation: J Pediatr. 1994 Jan;124(1):105-11
references.pmid: 8283358
references.citation: PLoS One. 2013;8(3):e58720
references.pmid: 23472217
references.citation: Cochrane Database Syst Rev. 2007 Oct 17;(4):CD002971
references.pmid: 17943776
references.citation: J Pediatr Surg. 2007 Mar;42(3):454-61
references.pmid: 17336180
references.citation: J Pediatr Surg. 1999 Oct;34(10):1453-7
references.pmid: 10549746
references.citation: Am J Surg. 1984 Jan;147(1):49-52
references.pmid: 6691551
references.citation: Am J Public Health. 1997 Dec;87(12):2026-31
references.pmid: 9431297
references.citation: Arch Dis Child Fetal Neonatal Ed. 2003 May;88(3):F209-13
references.pmid: 12719394
references.citation: Pediatrics. 1999 Apr;103(4 Pt 1):766-71
references.pmid: 10103300
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18758-63
references.pmid: 19022904
references.citation: N Engl J Med. 2011 Jan 20;364(3):255-64
references.pmid: 21247316
references.citation: Cytokine. 2011 Feb;53(2):249-55
references.pmid: 21145756
references.citation: Cochrane Database Syst Rev. 2011 Mar 16;(3):CD005496
references.pmid: 21412889
references.citation: Am J Obstet Gynecol. 2006 Sep;195(3):803-8
references.pmid: 16949415
references.citation: Am J Physiol Gastrointest Liver Physiol. 2012 Jul;303(1):G93-102
references.pmid: 22538401
references.citation: J Clin Invest. 2010 Aug;120(8):2989-3000
references.pmid: 20592468
references.citation: APMIS. 2003 Dec;111(12):1095-104
references.pmid: 14678018
references.citation: Clin Perinatol. 2004 Mar;31(1):143-55
references.pmid: 15183663
references.citation: Pediatr Pathol Lab Med. 1997 Jul-Aug;17(4):547-59
references.pmid: 9211547
references.citation: Pediatr Dev Pathol. 2003 Jan-Feb;6(1):6-23
references.pmid: 12424605
references.citation: J Surg Res. 2009 Nov;157(1):21-9
references.pmid: 19615694
references.citation: Semin Pediatr Surg. 1996 Aug;5(3):155-9
references.pmid: 8858761
references.citation: Pediatr Surg Int. 2003 Jul;19(5):326-30
references.pmid: 12764628
references.citation: J Pediatr. 2011 Dec;159(6):919-25.e3
references.pmid: 21798559
references.citation: J Pediatr. 2010 Nov;157(5):757-61
references.pmid: 20955849
references.citation: Pediatrics. 2010 Sep;126(3):443-56
references.pmid: 20732945
references.citation: Am J Physiol Gastrointest Liver Physiol. 2006 Apr;290(4):G757-64
references.pmid: 16269520
references.citation: Am J Obstet Gynecol. 2009 Dec;201(6):587.e1-8
references.pmid: 19729143
references.citation: Acta Paediatr. 2010 Mar;99(3):338-43
references.pmid: 19922507
references.citation: Gastroenterology. 2011 Jan;140(1):242-53
references.pmid: 20875417
references.citation: Ann Surg. 1978 Jan;187(1):1-7
references.pmid: 413500
references.citation: Pediatrics. 2009 Apr;123(4):1132-41
references.pmid: 19336372
references.citation: Cytokine. 2007 Dec;40(3):177-82
references.pmid: 18029191
references.citation: J Immunol Methods. 2008 Jul 20;336(1):78-84
references.pmid: 18495149
references.citation: Pediatr Res. 2004 Aug;56(2):240-9
references.pmid: 15181190