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.