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.
Conclusion
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.
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References
- Role of interleukin-6 in mortality from and physiologic response to sepsis.Infect Immunity. 2005; 73: 2751-2757
- Infectiological diagnostic problems in tertiary peritonitis.Langenbeck Arch Surg. 2006; 391: 473-482
- Tertiary peritonitis: clinical features of a complex nosocomial infection.World J Surg. 1998; 22: 158-163
- The epidemiology of intra-abdominal flora in critically ill patients with secondary and tertiary abdominal sepsis.Infection. 2009; 37: 522-527
- Identification of patients at risk for development of tertiary peritonitis on a surgical intensive care unit.J Gastrointest Surg. 2009; 13: 1358-1367
- Impact of microbial tolerance in persistent secondary Klebsiella pneumoniae peritonitis.Cytokine. 2011; 53: 84-93
- Microbial tolerance in secondary peritonitis is dose dependent.Cell Immunol. 2009; 258: 98-106
- Endogenous IL-10 leads to impaired bacterial clearance and reduced survival in a murine model of chronic peritonitis.Cytokine. 2007; 40: 207-215
- MicroRNAs: new helpers for surgeons?.Surgery. 2012; 151: 1-5
- Regulation of innate receptor pathways by microRNAs.Sci China Life Sci. 2013; 56: 13-18
- Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21.Nat Immunol. 2010; 11: 141-147
- Macrophage genetic reprogramming during chronic peritonitis is augmented by LPS pretreatment.J Surg Res. 2012; 175: 289-297
- A genomic storm in critically injured humans.J Exp Med. 2011; 208: 2581-2590
- A trio of microRNAs that control Toll-like receptor signalling.Int Immunol. 2011; 23: 421-425
- Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype.Nat Med. 2010; 16: 49-58
- Inositol phosphatase SHIP1 is a primary target of miR-155.Proc Natl Acad Sci USA. 2009; 106: 7113-7118
- Differential microRNA (miRNA) expression could explain microbial tolerance in a novel chronic peritonitis model.Innate Immunity. 2013; 19: 203-212
- Resolvin D1 receptor stereoselectivity and regulation of inflammation and proresolving microRNAs.Am J Pathol. 2012; 180: 2018-2027
- MicroRNAs in resolution of acute inflammation: identification of novel resolvin D1-miRNA circuits.FASEB J. 2011; 25: 544-560
- Six at six: interleukin-6 measured 6 h after the initiation of sepsis predicts mortality over 3 days.Shock. 2002; 17: 463-467
- Proinflammatory cytokines in peritonitis.J Med Life. 2011; 4: 158-162
- Interleukin 10 protects mice from lethal endotoxemia.J Exp Med. 1993; 177: 1205-1208
- Endogenous IL-10 protects mice from death during septic peritonitis.J Immunol. 1995; 155: 5397-5401
- MicroRNA-301a regulation of a T-helper 17 immune response controls autoimmune demyelination.Proc Natl Acad Sci USA. 2012; 109: E1248-E1257
- Serum microRNA signatures identified by Solexa sequencing predict sepsis patients' mortality: a prospective observational study.PloS One. 2012; 7: e38885
Article info
Publication history
Accepted:
June 26,
2013
Footnotes
This work supported by funding from the Veterans Affairs Merit Review Program.
Identification
Copyright
© 2013 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
