Interleukin-6, a marker of preservation injury in clinical lung transplantation

Interleukin-6 (IL-6) is one of the cytokines produced by human alveolar macrophages, lung parenchyma, and other cells in response to injury and infection. We hypothesized that IL-6 is released from poorly preserved lung grafts and may serve as a marker of preservation injury. Sixteen patients who received lung allografts were enrolled in this study. The average ischemic time was 284±78 minutes. Serum IL-6 level was measured before and at 4 and 24 hours after reperfusion of the grafts by an enzyme-linked immunosorbent assay. Preservation injury was assessed by (1) the need for prolonged intubation (>7 days), (2) the arterial/alveolar oxygen tension ratio (PaO₂/PAO₂ ratio) at 4 hours after graft reperfusion (only in heart-lung or double lung recipients), (3) the presence of diffuse alveolar damage on first lung biopsy, and (4) the 30-day graft survival rate. IL-6 level peaked at 4 hours after reperfusion and returned to baseline at 24 hours. The patients were divided into group I (n=6) and group II (n=10), depending on whether the 4-hour IL-6 level was more than 1000pg/ml or less than 500pg/ml, respectively. Group I patients required longer intubation (p<0.01) and had a lower PaO₂/PAO₂ ratio (p<0.001), more diffuse alveolar damage (p<0.01), and a lower graft survival rate (p<0.01) than those of group II. No bacterial, fungal, or viral infection was found during postoperative week 1 in either group. We conclude that the serum IL-6 level in the immediate postoperative period (4 hours) is a useful marker of preservation injury in clinical lung transplantation. An IL-6 level of more than 1000pg/ml is associated with poor outcome.