Increased levels of interleukin-1β and tumor necrosis factor-α in donor lungs rejected for transplantation.
BACKGROUND
Cytokine analysis of the donor lung shows significant promise as a strategy to biologically evaluate the organ before transplantation. This study compared gene expression levels of inflammatory cytokines between clinically rejected and transplanted donor lungs.


METHODS
Lung tissue biopsy specimens were taken from 17 clinically unsuitable lungs and 24 transplanted donor lungs before cold flush perfusion preservation. Expression levels of interleukin (IL)-6, IL-8, IL-10, interferon-γ, tumor necrosis factor (TNF)-α, and IL-1β messenger (m)RNA were measured in a blinded fashion by quantitative real-time reverse transcription polymerase chain reaction. Prospectively collected clinical data were analyzed retrospectively and compared with cytokine expression results. The primary end point was to examine the difference of expression levels of these cytokines between rejected donor lungs and lungs used for transplantation.


RESULTS
The ratio of partial pressure of oxygen/fraction of inspired oxygen, time on ventilation, infiltrates on chest X-ray images, and abnormal bronchoscopic findings for donors were statistically different between rejected and transplanted donor lungs. Comparison of gene expression levels showed that clinically rejected lungs had significantly higher levels of IL-1β and TNF-α than the lungs used for transplantation. Hierarchic clustering with IL-1β and TNF-α showed that 4 clinically unsuitable donor lungs had very low levels of these 2 cytokines.


CONCLUSIONS
Levels of IL-1β and TNF-α are significantly higher in donor lungs rejected for transplantation using clinical criteria. However, a sub-set of non-used lungs had low levels of IL-1β and TNF-α and thus could potentially have been used for transplantation. In the near future, these markers could be used to assist in the lung donor selection process and to monitor organ reparative strategies.
Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Research Institute, University Health Network, Toronto General Hospital, Ontario, Canada.
Marcelo
M
Cypel
Hiroyuki
H
Kaneda
Jonathan C
JC
Yeung
Masaki
M
Anraku
Kazuhiro
K
Yasufuku
Marc
M
de Perrot
Andrew
A
Pierre
Thomas K
TK
Waddell
Mingyao
M
Liu
Shaf
S
Keshavjee
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D005260:Female; D015870:Gene Expression; D006084:Graft Rejection; D006801:Humans; D053583:Interleukin-1beta / Q000032:analysis*; D008168:Lung / Q000473:pathology*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D015415:Biomarkers; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha