title: [The complement system: an old story or target of new therapeutic approaches?].
abstract: The complement system is a multifactorial protein cascade system which is essentially involved in the early unspecific immune response. Its major function is the activation of cellular defense mechanisms, opsonisation of foreign particles and the destruction of target cells. While the impact of the different complement components for bacterial elimination still remains controversial, overwhelming activation of the complement cascade, however, can induce life threatening tissue damage due to the effective cytotoxic properties. In the last years a variety of studies demonstrated beneficial, organ protective effects of complement modulation in models of severe inflammation. Attempts to control the complement system include the application of endogenous complement inhibitors e.g. C1-inhibitor (C1-INH) or the administration of recombinant complement receptors such as the soluble complement receptor 1 (rsCR1). Moreover antibodies against key proteins (C3, C5), against their activation products (C5a) or against complement receptor 3 (CR3, CD18/11b) mediated adhesion of leukocytes to the vascular endothelium, represent effective options of complement modulation. Besides this, insertion of membrane bound human complement regulators (DAF- CD55, MCP- CD46 or CD59) into xenogenic donor organs has proven effectiveness to prevent xenograft rejection. The described interventions protected from severe organ damage in various animal models of sepsis, myocardial and intestinal ischaemia-reperfusion injury, ARDS, nephritis, and xenograft rejection. With respect to recent clinical data, complement inhibition could represent a useful therapeutic strategy to control overwhelming inflammation. Own experiments demonstrated protective effects of complement modulation with C1 INH and rsCR1 in a model of complement induced pulmonary injury. With respect to sufficient host defense, however, the use of complement inhibitors must be considered carefully.
authors.affiliation: Klinik und Poliklinik für Anaesthesiologie und Intensivmedizin Universitätsklinikum Carl Gustav Carus Technische Universität Dresden. heller-a@rcs.urz.tu-dresden.de
authors.forename: A
authors.initials: A
authors.lastname: Heller
authors.forename: T
authors.initials: T
authors.lastname: Koch
mesh_terms: D003169:Complement Inactivator Proteins / Q000494:pharmacology / Q000627:therapeutic use; D003165:Complement System Proteins / Q000187:drug effects* / Q000502:physiology*; D006801:Humans
chemical_list: D003169:Complement Inactivator Proteins; D003165:Complement System Proteins