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

Nature Reviews Rheumatology volume 8, pages 522–533 (2012)Cite this article

Subjects

Abstract

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.

Key Points

  • Antimalarial agents are the cornerstone agents in the clinical management of systemic lupus erythematosus

  • Toll-like receptor (TLR)-antagonism has emerged as an important mechanism of action of antimalarial agents

  • The antilipidaemic, photoprotective and antiproliferative effects of chloroquine, hydroxychloroquine and quinacrine are in part explained by TLR antagonism

  • Antimalarial agents also act by several additional molecular mechanisms, the understanding of which continues to evolve

  • Antimalarial agents are generally safe, effective and clinically useful in almost all patients with systemic lupus erythematosus

  • These drugs offer considerable promise for treating a variety of immune-mediated as well as nonimmune diseases, and have exciting potential

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Figure 1
Figure 2: Role of antimalarial agents in TLR-mediated innate immune pathways in SLE.
Figure 3: Summary of TLR-independent mechanisms of antimalarial agents.

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Authors and Affiliations

  1. Division of Rheumatology, Cedars–Sinai Medical Center, 8700 Beverly Boulevard, Becker B-131, Los Angeles, 90048, CA, USA

    Daniel J. Wallace, Vineet S. Gudsoorkar, Michael H. Weisman & Swamy R. Venuturupalli

Authors
  1. Daniel J. Wallace
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  2. Vineet S. Gudsoorkar
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  3. Michael H. Weisman
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  4. Swamy R. Venuturupalli
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Contributions

D. J. Wallace, V. S. Gudsoorkar and S. R. Venuturupalli researched the data for the article. All authors provided a substantial contribution to discussions of the content and contributed equally to writing the article and to review and/or editing of the manuscript before submission.

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Correspondence to Daniel J. Wallace.

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The authors declare no competing financial interests.

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Wallace, D., Gudsoorkar, V., Weisman, M. et al. New insights into mechanisms of therapeutic effects of antimalarial agents in SLE. Nat Rev Rheumatol 8, 522–533 (2012). https://doi.org/10.1038/nrrheum.2012.106

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  • DOI: https://doi.org/10.1038/nrrheum.2012.106

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