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Cited by 16interferon and immune responsesSystemic Lupus Erythematosus ResearchImmune Response and Inflammation

Reappraisal of Antimalarials in Interferonopathies: New Perspectives for Old Drugs

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Piscianz, Elisa, Cuzzoni, Eva, Sharma, Rajan, Tesser, Alessandra, Sapra, Pooja, Tommasini, Alberto·2018·Current Medicinal Chemistry
DOI 10.2174/0929867324666170911162331
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Abstract

The story of antimalarials as antinflammatory drugs dates back several centuries. Chinin, the extract of the Cinchona bark, has been exploited since the 18th century for its antimalarial and antifebrile properties. Later, during the Second World War, the broad use of antimalarials allowed arguing their antirheumatic effect on soldiers. Since then, these drugs have been broadly used to treat Systemic Lupus Erythematosus, but, only recently, have the molecular mechanisms of action been partly clarified. Inhibitory action on vacuole function and trafficking has been considered for decades the main mechanism of the action of antimalarials, affecting the activation of phagocytes and dendritic cells. In addition, chloroquine is also known as a potent inhibitor of autophagy, providing another possible explanation of its antinflammatory action. However, much attention has been recently devoted to the action of antimalarials on the so-called cGASSTING pathway leading from the sensing of cytoplasmic nucleic acids to the production of type I interferons. This pathway is a fundamental mechanism of host defence, since it is able to detect microbial DNA and induce the type I interferon-mediated immune response. Of note, genetic defects in the degradation of nucleic acids lead to inappropriate cGAS-STING activation and inflammation. These disorders, called type I interferonopathies, represent a valuable model to study the antinflammatory potential of antimalarials. We will discuss possible development of antimalarials to improve the treatment of type I interferonopathies and likely multifactorial disorders characterised by interferon inflammation, such as Systemic Lupus Erythematosus.

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  • Some old drugs such as aspirin and antimalarials quinacrine and chloroquine inhibit cGAS, suggesting that downregulating this pathway might confer health benefits.

    “Interestingly, some old drugs such as aspirin146 and antimalarials quinacrine and chloroquine147 inhibit cGAS, further suggesting that downregulating this pathway might confer health benefits.”

    From The role of retrotransposable elements in ageing and age-associated diseases (2021) · cites this paper as [147]

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Authors
Piscianz, E., Cuzzoni, E., Sharma, R., Tesser, A., Sapra, P., & Tommasini, A.
Affiliations
  • University of Trieste (IT)
  • Head of Research and Content, ayurajan, India
  • Chaudhary Charan Singh University (IN)
  • IRCCS Materno Infantile Burlo Garofolo (IT)
Corresponding author
Tommasini, Alberto
ORCID
Venue
Current Medicinal Chemistry
Publisher
Bentham Science Publishers Ltd.
Published
2018-07-04
Volume
25
Issue
24
Pages
2797-2810
ISSN
0929-8673 (ISSN-L)
DOI
10.2174/0929867324666170911162331
OpenAlex
W2793235194
Cited by
15
References
84
Citations by year
2026: 2 · 2024: 1 · 2022: 1 · 2021: 3 · 2020: 5 · 2019: 1 · 2018: 2
FWCI
1.29
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Current Medicinal Chemistry (publishedVersion)
  • PubMed (publishedVersion)
  • ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion, other-oa)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
antimalarial drugs, type I interferonopathy, systemic lupus erythematosus, chloroquine, cGAS-STING pathway, autophagy inhibition, phagocyte activation, dendritic cells, interferonopathies, nucleic acid sensing
MeSH terms
Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase, Antimalarials, Autoimmune Diseases, Humans, Hydroxychloroquine, Interferon Type I, Lupus Erythematosus, Systemic, Nucleotidyltransferases, Rheumatic Diseases, Protein Serine-Threonine Kinases, Toll-Like Receptor 9

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