Interleukin-6 regulation of direct lung ischemia reperfusion injury.
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.
Farivar
Alexander S
AS
Division of Thoracic Surgery, University of Washington Medical Center, Seattle, Washington 98195, USA.
Merry
Heather E
HE
Fica-Delgado
Mauricio J
MJ
McCourtie
Anton S
AS
Mackinnon-Patterson
Brendan C
BC
Mulligan
Michael S
MS
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002199:Capillary Permeability / Q000187:drug effects; D018836:Inflammation Mediators / Q000032:analysis; D015850:Interleukin-6 / Q000627:therapeutic use*; D008168:Lung / Q000098:blood supply*; D010100:Oxygen / Q000097:blood; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D020318:Rats, Long-Evans; D011994:Recombinant Proteins / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000517:prevention & control*; D050796:STAT3 Transcription Factor / Q000378:metabolism
D018836:Inflammation Mediators; D015850:Interleukin-6; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; D009195:Peroxidase; D010100:Oxygen