Reduced hepatic transcription factor activation and expression of IL-6 and ICAM-1 after hemorrhage by NO scavening

C. Hierholzer*, T. R. Billiar, D. J. Tweardy, B. Harbrecht

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Background: Hemorrhagic shock (HS) elicits an inflammatory response characterized by increased cytokine production and recruitment of polymorphonucleated neutrophilic granulocytes (PMN) that we reported to be inducible nitric oxide synthase (iNOS) dependent. In a previous study, we demonstrated that removing excess induced nitric oxide (NO) by administration of the NO scavenger NOX resulted in reduced PMN infiltration, attenuated liver injury, and improved survival. In this study, we examined the role of NOX treatment in down-modulating the inflammatory response in the liver following HS. Methods: Rats (n=5) were subjected to severe HS with mean arterial blood pressure (MAP) of 40 mmHg for 100 min followed by resuscitation and killing at 24 h. Results: Shock animals demonstrated increased mRNA levels of interleukin (IL)-6 and intercellular adhesion molecule (ICAM)-1 and increased activation of the transcription factors nuclear factor kappa B (NF-κB) and signal transducers and activators of transcription 3 (Stat3). Treatment with NOX (30 mg/kg/h) infused 60 min following the onset of shock over 4 h resulted in significant reduction in cytokine mRNA expression and transcriptional factor activation. These results suggest that excessive NO contributes to hemorrhage-induced tissue inflammation and that reducing the bioavailability of NO using NOX may be beneficial in HS. Conclusion: These data indicate that NOX prevents liver injury in this HS model, possibly through down-modulation of proinflammatory signaling and the shock-induced inflammatory response.

Original languageEnglish
Pages (from-to)55-59
Number of pages5
JournalArchives of Orthopaedic and Trauma Surgery
Issue number2-3
StatePublished - Apr 2003
Externally publishedYes


  • Hemmorrhagic shock
  • Nitric oxide
  • Nitric oxide scavenger


Dive into the research topics of 'Reduced hepatic transcription factor activation and expression of IL-6 and ICAM-1 after hemorrhage by NO scavening'. Together they form a unique fingerprint.

Cite this