gms | German Medical Science

Einleitung: It is well known that Interferon-γ (IFN-γ) not only plays a critical role in antigen-dependent but in antigen-independent tissue injury, but it is not clear how tolerance induction affects the actions of IFN-γ in the transplant setting. To address this question, we compared the effects of IFN-γ on porcine recipients of syngeneic, rejecting and tolerant heart transplants.

Material und Methoden: IFN-γ was perfused continuously into the left anterior descending artery of hearts transplanted into three groups of MHC inbred miniature swine, each treated with a 12-day course of CyA. Group 1 recipients received a near syngeneic heart, Group 2 recipients received a class I disparate heart and Group 3 recipients were cotransplanted with a class I disparate heart and kidney, which uniformly induces tolerance to both grafts. An additional, group of animals were not transplanted but received intracoronary IFN-γ infusion into their native hearts.

Ergebnisse: IFN- perfusion not only accelerated the acute rejection of class I disparate hearts (mean survival time = 19±7.21 vs. 38±8.19, p=0.025) but caused near syngeneic, heart transplants, which otherwise survive indefinitely, to reject within 35 days (n=3) .In contrast, IFN-γ perfusion had no demonstrable effects on either interstitial rejection, the development of vascular lesions or graft survival in tolerant heart plus kidney allograft recipients (n=4) or in autologous hearts (n=2).

Schlussfolgerung: These results suggest that tolerance induction mitigates the damaging effects of IFN-γ itself and that the beneficial effects of tolerance induction on acute and chronic rejection may extend to antigen-independent factors like ischemia/reperfusion injury.