Taking complement to the clinic--has the time finally come?

Complement has been studied for over a century and its role in promoting the effector side of antibody-mediated immune reactions and of inducing inflammation is well understood. Nevertheless, it has proved surprisingly difficult to translate this information into pharmaceutical agents that can be used to treat immunopathological and inflammatory disease. There are, however, now clear signs that this situation will change. New types of therapeutic agents to interfere with complement function are being developed and it has become apparent quite recently that some common and otherwise untreatable diseases such as age-related macular degeneration are very largely due to mutations in the complement system that leads to a hyperinflammatory state. This has stimulated a renaissance of interest in the complement system as a therapeutic target and in this short review we discuss the possible ways of taking complement to the clinic, and the indications for which this may be carried out.