C1 inhibitor in anti-inflammatory therapy:: from animal experiment to clinical application

Potentially life-threatening consequences due to severe inflammatory tissue destruction are often closely associated with an excessive activation of the complement system. Various clinical disorders, including capillary leak syndrome, septic shock, multiple organ failure and hyperacute graft rejection are at least in part driven by an overactivated complement system. Therapeutic support of complement regulation appears to be a logical approach to reduce undesirable inflammatory reactions. C1 inhibitor, a multifunctional regulator af all major kinin-generating protein cascade systems, is frequently observed to be reduced in patients suffering from severe inflammation, due to ligand-induced inactivation of the regulatory protein. After C1 inhibitor has for many years been proven beneficial in acute treatment of hereditary angioedema, a growing number of reports now suggests that C1 inhibitor provides an effective means to protect against complement-mediated inflammatory tissue damage. These studies not only include pathophysiologically relevant animal models but also first attempts to prove the benefits of C1 inhibitor as a novel therapeutic approach in clinical trials. (C) 1999 Elsevier Science Ltd. All rights reserved.