C1-inhibitor and transplantation.

Excessive activation of the protein cascade systems has been associated with post-transplantation inflammatory disorders. There is increasing evidence that complement not only significantly contributes to ischemia/reperfusion injury upon cold storage of the organ but also, although to a different degree, to allograft rejection. Complement activation is most fulminant in hyperacute rejection but seems also to contribute to acute transplant rejection. Therapeutic substitution of appropriate regulators, therefore, appears to be a reasonable approach to reduce undesirable inflammatory reactions in the grafted organ. C1-inhibitor, a multifunctional regulator of the various kinin-generating cascade systems (for review see: E. Hack, chapter in this issue), is frequently reduced in patients suffering from severe inflammatory disorders. Studies applying pathophysiologically relevant animal models of allo- and xenotransplantation as well as promising first clinical results from successful allotransplantation now provide evidence that C1-inhibitor may also serve as an effective means to protect the grafted organ against inflammatory tissue injury. In xenotransplantation, complement inhibition by specific regulators such as C1-inhibitor may help to overcome hyperacute graft rejection. After a brief introduction on the significance of complement to allo- and xenotransplantation the following review will focus on the impact of C1-inhibitor treatment on transplantation-associated inflammatory disorders, where complement contributes to the pathogenesis.