TY - JOUR
T1 - Hydroxychloroquine in rheumatic autoimmune disorders and beyond
AU - Nirk, Eliise Laura
AU - Reggiori, Fulvio
AU - Mauthe, Mario
N1 - © 2020 The Authors. Published under the terms of the CC BY 4.0 license.
PY - 2020/8/7
Y1 - 2020/8/7
N2 - 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.
AB - 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.
KW - Arthritis, Rheumatoid/drug therapy
KW - Autoimmune Diseases/drug therapy
KW - Chloroquine
KW - Humans
KW - Hydroxychloroquine/therapeutic use
KW - Lupus Erythematosus, Systemic
UR - http://www.scopus.com/inward/record.url?scp=85088484346&partnerID=8YFLogxK
U2 - 10.15252/emmm.202012476
DO - 10.15252/emmm.202012476
M3 - Review
C2 - 32715647
SN - 1757-4676
VL - 12
SP - e12476
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
IS - 8
M1 - e12476
ER -