title: Poor outcome in bacterial peritonitis is associated with dysregulated microRNAs and an increased inflammatory response.
abstract: BACKGROUND
  Peritonitis is a common cause of surgical sepsis. The failure of the host to mount an appropriate immune response contributes to persistence of the infection. We investigated the role microRNAs may play in this failed immune response.
  
  
  METHODS
  Klebsiella pneumoniae was injected intraperitoneally in mice. Weight loss was used to predict clinical outcome. Peritoneal exudate cells (PECs) and supernatant were collected. RNA from PECs was run on screening microRNA array cards to determine gene expression, and validated by single assay analysis. Cytokine levels in supernatant were assayed by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Despite similar bacterial levels, PEC counts were higher in the predicted death group. The predicted deaths had higher levels of proinflammatory tumor necrosis factor-α/IL-6 and significantly lower levels of interleukin-10. MiR-221 was up-regulated in both the predicted death and predicted survivor groups. Five miRNAs were up-regulated in the predicted survivor group compared with normal controls.
  
  
  CONCLUSIONS
  Higher PEC counts and proinflammatory cytokines in the predicted death group indicates an exaggerated inflammatory response, with lower IL-10 levels despite similar bacterial counts. There were two dysregulated miRNAs with transcriptional targets that may explain our results. A more balanced immune response with an appropriate counter inflammatory response may be important for improving survival.
authors: Hiram C. Polk Jr. MD Department of Surgery, University of Louisville, Louisville, KY 40292, USA.
authors: Rebecca E
authors: RE
authors: Barnett
authors: Robert C
authors: RC
authors: Keskey
authors: John M
authors: JM
authors: Rao
authors: Adrian T
authors: AT
authors: Billeter
authors: Ziad
authors: Z
authors: Kanaan
authors: William G
authors: WG
authors: Cheadle
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D058491:Bacterial Load; D016207:Cytokines / Q000097:blood; D005786:Gene Expression Regulation; D007249:Inflammation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D010538:Peritonitis / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D016207:Cytokines; D035683:MicroRNAs; D051193:Toll-Like Receptors