Strategies of therapeutic complement inhibition.
The involvement of complement in the pathogenesis of a great number of partly life threatening diseases defines the importance to develop inhibitors which specifically interfere with its deleterious action. Endogenous soluble complement-inhibitors, antibodies or low molecular weight antagonists, either blocking key proteins of the cascade reaction or neutralizing the action of the complement-derived anaphylatoxins have successfully been tested in various animal models over the past years. Promising results consequently led to first clinical trials. This review is focused on different approaches for the development of inhibitors, on their site of action in the cascade, on possible indications for complement inhibition based on experimental animal data, and on potential side effects of such treatment.
Mollnes
Tom E
TE
Institute of Immunology, Rikshospitalet University Hospital and University of Oslo, N-0027 Oslo, Norway. t.e.mollnes@labmed.uio.no
Kirschfink
Michael
M
D000706:Anaphylatoxins / Q000037:antagonists & inhibitors*; D000818:Animals; D002986:Clinical Trials as Topic; D003167:Complement Activation / Q000187:drug effects*; D004195:Disease Models, Animal; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans
D000706:Anaphylatoxins; D004791:Enzyme Inhibitors