title: Control of innate immunological mechanisms as a route to drug minimization.
abstract: OBJECTIVE
  Much research in transplantation focuses on treatments for rejection and induction of tolerance. Recent evidence has shown that initial inflammation induced by innate immune effectors after transplantation has a key role in modulating adaptive immune responses that cause organ rejection. Here, we describe the role of the innate immune system, particularly the complement activation pathways, and how they influence adaptive immune responses post-transplantation and current strategies, which are under development to block these innate pathways.
  
  
  RESULTS
  Anaphylatoxins and their respective receptors are proving to be important in T-cell-mediated immunity and make attractive targets for therapies designed to promote tolerance in solid organ transplantation. Additionally, regulators of complement activation are currently being tested in clinical trials, with improvements in drug delivery.
  
  
  CONCLUSIONS
  Preventing ischaemia-reperfusion injury in transplanted organs significantly reduces immune activation and promotes graft survival. Research into the mechanisms of complement activation in both native organ ischaemia and transplantation models detail emerging roles for complement intermediates that can serve as targets for intervention, with the aim of reducing early post-transplant inflammation, reducing the intensity of immunosuppressive regimens, leading to prolonged graft survival.
authors.affiliation: MRC Centre for Transplantation, Division of Transplantation Immunology and Mucosal Biology, King's College London School of Medicine, Guy's Hospital, London, UK.
authors.forename: Elham
authors.initials: E
authors.lastname: Asgari
authors.forename: Conrad A
authors.initials: CA
authors.lastname: Farrar
authors.forename: Steven H
authors.initials: SH
authors.lastname: Sacks
mesh_terms: D000818:Animals; D003167:Complement Activation / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology / Q000502:physiology; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007113:Immunity, Innate; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000276:immunology / Q000517:prevention & control
chemical_list: D007166:Immunosuppressive Agents; D003165:Complement System Proteins