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Published on: July 7, 2017
Temporal Changes of Inflammatory Cytokine Profiles in Epithelial Lining Fluid in a Canine Lung Transplant Model
Atsushi Wada, Mitsutomo Kohno1, Kana Oiwa
1Division of General Thoracic Surgery, Department of Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan. kohno@1993.jukuin.keio.ac.jp.
Insights
Lung transplant reperfusion injury shows specific changes in cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). These temporal shifts in the epithelial lining fluid (ELF) may explain post-transplant lung dysfunction.
Area of Science:
- Immunology
- Transplantation Science
- Respiratory Medicine
Background:
- Ischemia-reperfusion injury (IRI) is a major cause of post-transplant lung dysfunction.
- The complex network of cytokines involved in lung IRI is not fully understood.
- Epithelial lining fluid (ELF) offers a direct source for analyzing local inflammatory responses in the lungs.
Purpose of the Study:
- To investigate temporal changes in cytokine levels within the ELF of a canine lung transplantation model.
- To correlate these cytokine changes with the development of lung injury following ischemia-reperfusion.
- To identify specific cytokine profiles associated with post-transplant lung dysfunction.
Main Methods:
- A left single-lung transplantation model in canines was used with an 18-hour ischemic time to induce lung injury.
- Bronchoscopic microsampling was employed for serial collection of ELF from distal airways, hourly up to 5 hours post-reperfusion.
- Levels of pro-inflammatory cytokines were compared between the transplant group and a sham-operated control group, as well as against baseline.
Main Results:
- Concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) significantly increased immediately post-reperfusion in the transplant group compared to controls (P < 0.005 and P < 0.05, respectively).
- Elevated levels of TNF-α and IL-6 were sustained throughout the 5-hour observation period.
- Interferon-gamma (IFN-γ) levels showed a significant decrease 3 hours after reperfusion initiation (P < 0.05).
Conclusions:
- Distinct, time-dependent alterations in TNF-α, IL-6, and IFN-γ were observed in the ELF following lung transplantation.
- These specific changes in the cytokine profile within the ELF are potentially linked to the underlying mechanisms of post-transplant lung dysfunction.
- Further research into these cytokine dynamics could inform therapeutic strategies to mitigate lung IRI.
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.
