Complement and clinical intervention.
The nine major components of the complement protein system are normally activated in sequence by antigen-antibody complexes, initiating the inflammatory response. The clinical manifestations arise mainly from the release of histamine, mediated by anaphylatoxin action on mast cells. In rampant infection, this classical pathway is enhanced by further activation of complement C3 through a specific enzyme loop, the alternative pathway. Unfortunately the complexity of the complement system makes it vulnerable to external interference, particularly to man's intervention both through the administration of intravenous "drugs" and by certain surgical procedures. This results in gross systemic activation of complement, particularly C3 giving rise to anaphylactoid shock. More recently, direct activation of complement C5 has been reported, particularly as a result of polytrauma. This has consequences on polymorphonuclear leucocyte behaviour and is likely to be involved in adult respiratory distress syndrome (ARDS). Similarly, excessive activation of C3 may stimulate disseminated intravascular coagulation (DIC) rather than immediate anaphylactoid response. The clinical outcome of complement activation appears to depend upon the rate of activation and its extent, as well as upon the particular component involved. In immediate reactions, complement may be involved in both immune and non-immune activations. Bias to certain pathways is revealed by certain drugs or procedures, and practical methods of evaluating reaction mechanisms are discussed. Despite the high incidence of complement involvement in immediate reactions, there are no useful screening pointers to the patient "at risk". Delayed effects have received little attention. Although C3 conversion is certainly associated with DIC, its predictive value in a clinical trial was not very great.(ABSTRACT TRUNCATED AT 250 WORDS)
D000707:Anaphylaxis / Q000276:immunology; D000777:Anesthetics / Q000494:pharmacology; D002986:Clinical Trials as Topic; D003167:Complement Activation; D003176:Complement C3 / Q000032:analysis; D003182:Complement C5 / Q000032:analysis; D003165:Complement System Proteins / Q000032:analysis / Q000502:physiology*; D004211:Disseminated Intravascular Coagulation / Q000276:immunology; D006801:Humans; D011446:Prospective Studies; D012306:Risk
D000777:Anesthetics; D003176:Complement C3; D003182:Complement C5; D003165:Complement System Proteins