CYTOKINE INTERLEUKIN-2, TUMOR-NECROSIS-FACTOR-ALPHA, AND INTERFERON-GAMMA RELEASE AFTER ISCHEMIA-REPERFUSION INJURY IN A NOVEL LUNG AUTOGRAFT ANIMAL-MODEL

Previously, we have reported an increase in the cytokines interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) early after left lung allotransplantation in dogs. The purpose of this study was to develop a novel model of canine lung autotransplantation and to observe whether ischemia/reperfusion injury alone (in the absence of an allogenic stimulus) would result in this cytokine release as seen in the allograft. Thus, using this model, early changes in cellular and cytokine composition in the lung autograft were monitored through the use of bronchoalveolar lavage (BAL) and plasma. The effects of ischemia/reperfusion injury on lung histology and major histocompatibility class II (MHC II) antigen expression were also observed. Ten mongrel dogs were subjected to left lung autotransplantation. Lungs were stored cold for 4 h, with a warm ischemic time of 1 h. BAL, blood, and biopsy specimens were taken preoperatively and 1 h, 4 h, 24 h, and 1 wk postoperatively. The mean BAL IL-2 levels significantly rose from a preoperative value of 150 +/- 19 pg/ml to 246 +/- 67 pg/ml 4 h after transplantation (p < 0.05), decreasing to preoperative levels after 24 h (128 +/- 54 pg/ml). Plasma levels of IL-2 did not change from preoperative values. In contrast to IL-2, TNF-alpha and IFN-gamma did not change in either BAL or plasma of the autograft. BAL total cell counts demonstrated a significant neutrophil influx in the autograft at 1, 4, and 24 h postoperatively (preoperative: 1.8 +/- 0.56 x 10(3) cells/ml; 1 h: 31 +/- 20 x 10(4) cells/ml; 4 h: 15 +/- 7.4 x 10(4) cells/ml; 24 h: 17 +/- 5.2 x 10(4) cells/ml) (p < 0.05), while the total number of lymphocytes and macrophages remained relatively constant. Histology revealed a relatively normal lung with slight inflammation at 4 and 24 h that began to resolve after 1 wk. However, there was evidence of MHC II antigen expression on lung epithelium after 1 wk. We conclude that short periods of ischemia can result in the early release of IL-2 that occurs in the absence of an allogeneic stimulus and that ischemia/reperfusion injury may be a potential inducer of MHC II antigen expression.