Interleukin-6 Infusion Blunts Proinflammatory Cytokine Production Without Causing Systematic Toxicity in a Swine Model of Uncontrolled Hemorrhagic Shock
Abstract
Background: Serum elevations of in- terleukin-6 (IL-6) correlate with multiple organ dysfunction syndrome and mortality in critically injured trauma patients. Data from rodent models of controlled hemorrhage suggest that recombinant IL-6 (rIL-6) infusion protects tissue at risk for ischemia reperfusion injury. Exogenous rIL-6 administered during shock appears to abrogate inflammation, providing a protective rather than a deleterious influence. In an examination of this paradox, the current study aimed to determine whether rIL-6 decreases inflammation in a clinically relevant large animal model of uncontrolled hemorrhagic shock, (UHS), and to investigate the mechanism of protection. Methods: Swine were randomized to four groups (8 animals in each): (1) sacrifice, (2) sham (splenectomy followed by hemodilution and cooling to 33 Degrees C), (3) rIL-6 infusion (sham plus UHS using grade 5 liver injury with packing and resuscitation plus blinded infusion of rIL-6 [10 mcg/kg]), and (4) placebo (UHS plus blinded vehicle). After 4 hours, blood was sampled, estimated blood loss determined, animals sacrificed, and lung harvested for RNA isolation. Quantitative reverse transcriptase-polymerase chain reaction was used to assess granulocyte colony-stimulating factor (G-CSF), IL-6, and tumor necrosis factor- (TNF-alpha ) messenger ribonucleic acid (mRNA) levels. Serum levels of IL-6 and TNF-alpha were measured by en- zyme-linked immunoassay (ELISA). Results: As compared with placebo, IL-6 infusion in UHS did not increase estimated blood loss or white blood cell counts, nor decrease hematocrit or plate- let levels. As compared with the sham condition, lung G-CSF mRNA production in UHS plus placebo increased eightfold (* p less than 0.05). In contrast, rIL-6 infusion plus UHS blunted G-CSF mRNA levels, which were not significantly higher than sham levels (p = 0.1).
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2004
- Accession Number
- ADA630478
Entities
People
- D. A. Spain
- D. J. Tweardy
- J. B. Holcomb
- J. C. Lam
- J. M. Macaitis
- M. A. Mastrangelo
- N. A. Zautke
- Susan I. Brundage
Organizations
- United States Army Institute of Surgical Research