THE EARLY RELEASE OF INTERLEUKIN-2, TUMOR-NECROSIS-FACTOR-ALPHA AND INTERFERON-GAMMA AFTER ISCHEMIA-REPERFUSION INJURY IN THE LUNG ALLOGRAFT

A period of cold and warm ischemia is obligatory when performing lung transplantation. Subtle ischemia-reperfusion injury induced in the cou rse of transplantation can pass undetected or cause a short phase of r eversible lung dysfunction. We hypothesized that ischemia-reperfusion injury may result in the local release of cytokines that have the capa bility to mediate acute lung injury early following transplantation. T o test this hypothesis, 10 mongrel dogs were subjected to left lung al lotransplantation. As performed in the clinical setting, donor lungs w ere preserved with Eurocollins solution and stored at 4 degrees C for 4 hr, which was followed by 1 hr of warm ischemia. Recipients received standard immunosuppression of cyclosporine, azathioprine, and low dos e steroids. Bronchoalveolar lavage (BAL) and open lung biopsies were p erformed before operation and at approximately 1 hr, 4 hr, 24 hr, and 1 week after transplantation. A significant increase in BAL IL-2 level s was observed 4 hr after surgery (0 hr: 349+/-138 pg/ml; 4 hr: 757+/- 284 pg/ml) (mean +/- SEM) (P<0.05) which subsequently decreased 24 hr (320+/-168 pg/ml) after transplantation. BAL TNF-alpha levels were sig nificantly increased 1 hr after transplantation (P<0.05) (0 hr: 3.4+/- 0.65 pg/ml; 1 hr: 13.3+/-8.0 pg/ml) returning to baseline after 24 hr (5.8+/-2.8 pg/ml). BAL IFN-gamma levels also significantly increased 1 and 4 hr after transplantation (0 hr: 7.2+/-2.1 pg/ml; 1 hr: 68.2+/-4 9.2 pg/ml; 4 hr: 301+/-131 pg/ml) (P<0.05). This decreased back to bas eline after 24 hr and 1 week (5.2+/-1.2 pg/ml and 9.7+/-7.9 pg/ml, res pectively). There were no changes detected in plasma levels of cytokin es. Histology showed evidence of grade 1-2 rejection after 1 week. We conclude that subjection of a lung allograft to standard periods of co ld-warm ischemia will result in a temporary early elevation of IL-2, T NF-alpha, and IFN-gamma detectable only in the bronchoalveolar compart ment. Such local increase in cytokines in the lung allograft may play an important role in the development of early allograft dysfunction.