New insights into mechanisms of therapeutic effects of antimalarial agents in SLE

Nat Rev Rheumatol. 2012 Sep;8(9):522-33. doi: 10.1038/nrrheum.2012.106. Epub 2012 Jul 17.


Antimalarial agents have routinely been used for the treatment of systemic lupus erythematosus (SLE) for over 50 years. These agents continue to enjoy success as the initial pharmacotherapy for SLE even in the era of targeted therapies. Antimalarial agents have numerous biological effects that are responsible for their immunomodulatory actions in SLE. Their inhibitory effect on Toll-like receptor-mediated activation of the innate immune response is perhaps the most important discovery regarding their putative mechanism of action, but some other, previously known properties, such as antithrombotic and antilipidaemic effects, are now explained by new research. In the 1980s and 1990s, these antihyperlipidaemic and antithrombotic effects were demonstrated in retrospective clinical studies, and over the past few years prospective studies have confirmed those findings. Knowledge about the risk-benefit profile of antimalarial agents during pregnancy and lactation has evolved, as has the concept of retinal toxicity. Antimalarial agents have unique disease-modifying properties in SLE and newer iterations of this class of anti-inflammatory agents will have a profound effect upon the treatment of autoimmune disease.

Publication types

  • Review

MeSH terms

  • Adult
  • Antimalarials / pharmacokinetics
  • Antimalarials / therapeutic use*
  • Female
  • Fibrinolytic Agents / therapeutic use
  • Half-Life
  • Humans
  • Hypolipidemic Agents / therapeutic use
  • Immunity, Innate / drug effects
  • Immunologic Factors / pharmacokinetics
  • Immunologic Factors / therapeutic use*
  • Lactation / drug effects
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / pathology
  • Lupus Erythematosus, Systemic / physiopathology
  • Pregnancy
  • Pregnancy Complications / drug therapy
  • Risk Assessment
  • Toll-Like Receptors / drug effects
  • Toll-Like Receptors / metabolism
  • Treatment Outcome


  • Antimalarials
  • Fibrinolytic Agents
  • Hypolipidemic Agents
  • Immunologic Factors
  • Toll-Like Receptors