A nitric oxide scavenger protects against pulmonary inflammation following hemorrhagic shock

Christian Hierholzer, John M. Menezes, Andreas Ungeheuer, Timothy R. Billiar, David J. Tweardy, Brian G. Harbrecht*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Hemorrhagic shock (HS) elicits an inflammatory response characterized by increased cytokine production and recruitment of PMN which we previously found to be iNOS dependent. In this study we attempted to remove excess induced-NO by administration of the NO scavenger, NOX, with the goal of suppressing proinflammatory signaling and reducing organ damage. Rats subjected to HS (MAP = 40 mmHg for 100 min) followed by resuscitation and examined 24 h later demonstrated histological signs of lung injury including pulmonary edema as well as an 8.6-fold increase in MPO-positive PMN. These events were accompanied by a 3.9-fold increase in mRNA levels for IL-6, 3.7-fold for ICAM-1, 3.5-fold for IL-1β, and 7.3-fold for TNFα compared to sham animals. Immunostaining of the lungs of shock animals demonstrated IL-6 protein localized to cells lining the luminal sides of bronchiols. These animals also demonstrated a 2-fold and 5.5-fold increase in activation of NF-κB and Stat3 (an IL-6 signaling intermediate), respectively. Administration of NOX (30 mg/kg/h beginning at 60 min of shock for total of 4.5 h) resulted in reduced lung injury as measured by a 46% reduction in PMN infiltration, a 20% decrease in wet-to-dry ratio, and improved arterial blood gases. NOX reduced proinflammatory signaling in the lung as demonstrated by a 62% decrease in NF-κB binding, 47% reduction in Stat3 binding, a reduction in mRNA expression of 48% for IL-6, 57% for ICAM-1, 67% for IL-1β, and 64% for TNFα, as well as a marked reduction in the intensity of IL-6 protein staining. These data indicate that NOX prevents lung injury in this HS model, possibly through downmodulation of proinflammatory signaling and the shock-induced inflammatory response.

Original languageEnglish
Pages (from-to)98-103
Number of pages6
Issue number2
StatePublished - Feb 2002
Externally publishedYes


  • Cytokines
  • Lung injury
  • NF-κB
  • STAT
  • Transcription factor


Dive into the research topics of 'A nitric oxide scavenger protects against pulmonary inflammation following hemorrhagic shock'. Together they form a unique fingerprint.

Cite this