Targeting the complement system

Interest has blossomed in the development of complement inhibitors, in para llel with a growth in our understanding of the biology of the complement ca scade. The first generation of designed inhibitors was based on naturally o ccurring complement receptors and regulatory molecules. These agents provid ed useful tools for exploring the role of complement in experimental models of disease, but may have limited therapeutic application in humans because of their short half-lives, limited bioavailability and possible antigenici ty, More recently, humanized antibodies and synthetic molecules that block the activation of complement have been developed, which look as though they may overcome some of these difficulties, The possibility for precision inh ibition of a limited part of the complement cascade, or for inhibition conf ined to a single organ, may offer effective therapeutic results, while avoi ding the disadvantages of nonselective complement blockade. This review exa mines the recent evidence that complement inhibition will reduce tissue dam age resulting from organ transplantation, ischaemia-reperfusion injury, can cer, glomerulonephritis and the use of extracorporeal circuits. Curr Opin N ephrol Hypertens 8:557-562. (C) 1999 Lippincott Williams & Wilkins.