PubMed1997
Inappropriate or excessive activation of the complement system can lead to harmful, potentially life-threatening consequences due to severe inflammatory tissue destruction. These consequences are clinically manifested in various disorders, including septic shock, multiple organ failure and hyperacute graft rejection. Genetic complement deficiencies or complement depletion have been proven to be beneficial in reducing tissue injury in a number of animal models of severe complement-dependent inflammation. It is therefore believed that therapeutic inhibition of complement is likely to arrest the process of certain diseases. Attempts to efficiently inhibit complement include the application of endogenous soluble complement inhibitors (C1-inhibitor, recombinant soluble complement receptor 1- rsCR1), the administration of antibodies, either blocking key proteins of the cascade reaction (e.g. C3, C5), neutralizing the action of the complement-derived anaphylatoxin C5a, or interfering with complement receptor 3 (CR3, CD18/11b)-mediated adhesion of inflammatory cells to the vascular endothelium. In addition, incorporation of membrane-bound complement regulators (DAF-CD55, MCP-CD46, CD59) has become possible by transfection of the correspondent cDNA into xenogeneic cells. Thereby, protection against complement-mediated inflammatory tissue damage could be achieved in various animal models of sepsis, myocardial as well as intestinal ischemia/reperfusion injury, adult respiratory distress syndrome, nephritis and graft rejection. Supported by results from first clinical trials, complement inhibition appears to be a suitable therapeutic approach to control inflammation. Current strategies to specifically inhibit complement in inflammation have been discussed at a recent meeting on the 'Immune Consequences of Trauma, Shock and Sepsis', held from March 4-8, 1997, in Munich, Germany. The Congress (chairman: E. Faist, Munich, Germany), which was held in close cooperation with various national and international shock and trauma societies, was attended by about 2000 delegates from 40 countries. The major objective of the meeting was to provide an overview on the most state-of-the-art methods to prevent multiple organ dysfunction syndrome (MODS)/multiple organ failure (MOF) following the systemic inflammatory response (SIRS) to severe trauma. One of the largest symposia held within the Congress was devoted to current aspects of controlling complement in inflammation (for abstracts see: Shock 1997, 7 Suppl., 71-75). After providing the audience with information on the scientific background by addressing the clinical relevance of complement activation (G.O. Till, Ann Arbor, MI, USA) and discussing recent developments in modern complement diagnosis (J. Köhl, Hannover, Germany), B.P. Morgan (Cardiff, UK) introduced the symposium's special issue by giving an overview on complement regulatory molecules. Selected topics included overviews on the application of C1 inhibitor (C.E. Hack, Amsterdam, NL), sCR1 (U.S. Ryan, Needham, MA, USA), antibodies to C5 (Y. Wang, New Haven CT, USA) and to the anaphylatoxin C5a (M. Oppermann, Göttingen, Germany), and a report on complement inhibition in cardiopulmonary bypass (T.E. Mollnes, Bodø, Norway). The growing interest of clinicians in complement-directed anti-inflammatory therapy, and the fact that only some of the various aspects of therapeutic complement inhibition could be addressed on the meeting, has motivated the author to expand a Congress report into a short comprehensive review on recent strategies to control complement in inflammation.