Interleukin-6 regulation of direct lung ischemia reperfusion injury
AS Farivar, HE Merry, MJ Fica-Delgado… - The Annals of thoracic …, 2006 - Elsevier
AS Farivar, HE Merry, MJ Fica-Delgado, AS McCourtie, BC Mackinnon-Patterson…
The Annals of thoracic surgery, 2006•ElsevierBACKGROUND: 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 …
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 …
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.
Elsevier