Interleukin-6 regulation of direct lung ischemia reperfusion injury

Ann Thorac Surg. 2006 Aug;82(2):472-8. doi: 10.1016/j.athoracsur.2006.03.060.


Background: Lung ischemia reperfusion injury continues to adversely affect patient and graft survival after transplantation. While the role of interleukin-6 has been studied in ischemia-reperfusion models of intestine, liver, and heart, its participation in lung reperfusion injury has not been characterized.

Methods: We administered recombinant interleukin-6 to rat lungs through the intratracheal route before inducing left lung ischemia and reperfusion. Multiple in-vivo indicators of left lung injury were studied, as were transactivation patterns for nuclear factor kappa B and signal transduction and activators of transcription-3. Downstream effects on the elaboration of proinflammatory chemokines and cytokines were also studied.

Results: Recombinant interleukin-6 reduced endothelial disruption and neutrophil sequestration in left lung and alveolar spaces, resulting in improved oxygenation after ischemia and 4 hours of reperfusion. This protection was associated with decreased nuclear factor kappa B and signal transduction and activators of transcription-3 nuclear translocation early in reperfusion, and diminished proinflammatory mediator secretion late in reperfusion.

Conclusions: Further studies focusing on the effects of recombinant interleukin-6 in large animal models are warranted, as this may be a novel strategy to improve outcomes after lung transplantation. Intratracheal administration may focus its efficacy on the lung while reducing effects on other organ systems during organ procurement.

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Capillary Permeability / drug effects
  • Inflammation Mediators / analysis
  • Interleukin-6 / therapeutic use*
  • Lung / blood supply*
  • Oxygen / blood
  • Peroxidase / analysis
  • Rats
  • Rats, Long-Evans
  • Recombinant Proteins / therapeutic use
  • Reperfusion Injury / prevention & control*
  • STAT3 Transcription Factor / metabolism


  • Inflammation Mediators
  • Interleukin-6
  • Recombinant Proteins
  • STAT3 Transcription Factor
  • Peroxidase
  • Oxygen