Title:Reappraisal of Antimalarials in Interferonopathies: New Perspectives for Old Drugs
Volume: 25
Issue: 24
Author(s): Elisa Piscianz, Eva Cuzzoni, Rajan Sharma, Alessandra Tesser, Pooja Sapra and Alberto Tommasini*
Affiliation:
- Department of Paediatrics, Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste,Italy
Keywords:
Antimalarials, Autoimmunity, Autoinflammatory diseases, Interferonopathies, Interferon Signature,
Cyclic GMP-AMP Synthase, Systemic Lupus Erythematosus, Type I Interferons.
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.
