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.