Control of innate immunological mechanisms as a route to drug minimization

Curr Opin Organ Transplant. 2014 Aug;19(4):342-7. doi: 10.1097/MOT.0000000000000094.

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Complement Activation / immunology
  • Complement System Proteins / immunology
  • Complement System Proteins / physiology
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Humans
  • Immunity, Cellular / immunology
  • Immunity, Innate*
  • Immunosuppressive Agents / therapeutic use*
  • Reperfusion Injury / immunology
  • Reperfusion Injury / prevention & control

Substances

  • Immunosuppressive Agents
  • Complement System Proteins