Temporal Changes of Inflammatory Cytokine Profiles in Epithelial Lining Fluid in a Canine Lung Transplant Model

Tokai J Exp Clin Med. 2017 Dec 20;42(4):165-175.

Abstract

Objectives: Ischemia-reperfusion injury resulting in post-transplant lung dysfunction involves a complicated network of cytokines that has yet to be fully investigated. We analyzed temporal changes in cytokine levels in epithelial lining fluid (ELF) from the distal airways of a canine lung transplantation model.

Methods: Ischemic time was set to 18 hours to enhance lung injury in a left single-lung transplantation model. ELF was collected via bronchoscopic microsampling, a minimally-invasive technique allowing repeated sampling, hourly up to 5 hours after reperfusion started. We compared levels of pro-inflammatory cytokines in ELF with those at baseline (time zero), and with a sham-operated control group.

Results: Concentrations of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) significantly increased immediately after the start of lung reperfusion in the transplant group relative to the sham group (P < 0.005 and P < 0.05, respectively); both were sustained through the 5 hours. Interferon gamma (IFN-γ levels were significantly reduced 3 h after reperfusion started (P < 0.05).

Conclusions: We found time- and cytokine-dependent changes in TNF-α, IL-6, and IFN-γ in ELF from the lung transplantation model. These specific changes in the cytokine profile may relate to the mechanism underlying post-transplant lung dysfunction.

MeSH terms

  • Animals
  • Dogs
  • Inflammation Mediators / metabolism*
  • Interferon-gamma / metabolism*
  • Interleukin-6 / metabolism*
  • Lung / metabolism*
  • Lung Transplantation*
  • Models, Animal
  • Reperfusion Injury / metabolism
  • Respiratory Mucosa / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Inflammation Mediators
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma