title: Remote thermal injury increases LPS-induced intestinal IL-6 production.
abstract: BACKGROUND
  Patients suffering from burn injury are at high risk for subsequent infection. Thermal injury followed by endotoxemia may result in a "second hit," causing an exaggerated inflammatory response with increased morbidity and mortality. The role of the intestine in this "second hit" response is unknown. We hypothesized that remote thermal injury increases the inflammatory response of intestinal mucosa to subsequent treatment with lipopolysaccharide (LPS).
  
  
  METHODS
  Mice underwent sham or scald injury. Seven days after injury, mice were treated with LPS. Blood and bowel specimens were obtained. Serum and intestinal inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Changes in TLR-4 pathway components in intestine were measured by reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and electrophoretic mobility shift assay (EMSA). Intestinal leukocyte infiltration was analyzed by myeloperoxidase assay.
  
  
  RESULTS
  A "second hit" of injected LPS resulted in increased IL-6 in intestine of burned mice compared with sham. Similarly, jejunal IL-6 mRNA levels increased in mice with prior thermal injury, suggesting a transcriptional mechanism. Of transcription factors known to drive IL-6 expression, only AP-1 activation was significantly elevated by a "second hit" of LPS.
  
  
  CONCLUSIONS
  Prior thermal injury potentiates LPS-induced IL-6 cytokine production in intestine. These results indicate a heightened inflammatory response to a second hit by intestine after burn injury.
authors.affiliation: The Shriners Hospitals for Children-Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Huber
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Bailey
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Schuster
authors.forename: Cora K
authors.initials: CK
authors.lastname: Ogle
authors.forename: Alex B
authors.initials: AB
authors.lastname: Lentsch
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Pritts
mesh_terms: D000818:Animals; D002056:Burns / Q000276:immunology* / Q000503:physiopathology; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000276:immunology; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D007583:Jejunum / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D018808:Transcription Factor AP-1