Hydroxychloroquine in rheumatic autoimmune disorders and beyond

Eliise Laura Nirk, Fulvio Reggiori, Mario Mauthe*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

78 Citations (Scopus)
221 Downloads (Pure)

Abstract

Initially used as antimalarial drugs, hydroxychloroquine (HCQ) and, to a lesser extent, chloroquine (CQ) are currently being used to treat several diseases. Due to its cost-effectiveness, safety and efficacy, HCQ is especially used in rheumatic autoimmune disorders (RADs), such as systemic lupus erythematosus, primary Sjögren's syndrome and rheumatoid arthritis. Despite this widespread use in the clinic, HCQ molecular modes of action are still not completely understood. By influencing several cellular pathways through different mechanisms, CQ and HCQ inhibit multiple endolysosomal functions, including autophagy, as well as endosomal Toll-like receptor activation and calcium signalling. These effects alter several aspects of the immune system with the synergistic consequence of reducing pro-inflammatory cytokine production and release, one of the most marked symptoms of RADs. Here, we review the current knowledge on the molecular modes of action of these drugs and the circumstances under which they trigger side effects. This is of particular importance as the therapeutic use of HCQ is expanding beyond the treatment of malaria and RADs.

Original languageEnglish
Article number12476
Number of pages17
JournalEMBO Molecular Medicine
Volume12
Issue number8
DOIs
Publication statusPublished - 26-Jul-2020

Keywords

  • calcium
  • chloroquine
  • cytokines
  • lysosome
  • toll-like receptors
  • SYSTEMIC-LUPUS-ERYTHEMATOSUS
  • PRIMARY SJOGRENS-SYNDROME
  • GMP-AMP SYNTHASE
  • CANCER STEM-CELLS
  • ANTIGEN-PRESENTING CELLS
  • NECROSIS-FACTOR-ALPHA
  • REGULATORY T-CELLS
  • ANTIMALARIAL-DRUGS
  • BREAST-CANCER
  • IN-VITRO

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