The Role of Chloroquine and Hydroxychloroquine in Immune Regulation and Diseases

Abstract

<jats:sec> <jats:title>:</jats:title> <jats:p>Chloroquine (CQ) and hydroxychloroquine (HCQ) are derivatives of the heterocyclic aromatic compound quinoline. These economical compounds were used as antimalarial agents for many years. Currently, they are used as monotherapy or in conjunction with other therapies for the treatment of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS) and antiphospholipid antibody syndrome (APS). Based on its effects on the modulation of the autophagy process, various clinical studies suggest that CQ and HCQ could be used in combination with other chemotherapeutics for the treatment of various types of cancer. Furthermore, the antiviral effects showed against Zika, Chikungunya, and HIV are due to the annulation of endosomal/lysosomal acidification. Recently, CQ and HCQ were approved for The U.S. Food and Drug Administration (FDA) for the treatment of infected patients with the coronavirus SARS-CoV-2, causing the disease originated in December 2019, namely COVID-2019. Several mechanisms have been proposed to explain the pharmacological effects of these drugs: 1) disruption of lysosomal and endosomal pH, 2) inhibition of protein secretion/expression, 3) inhibition of antigen presentation, 4) decrease of proinflammatory cytokines, 5) inhibition of autophagy, 6) induction of apoptosis and 7) inhibition of ion channels activation. Thus, evidence has shown that these structures are leader molecules that can be modified or combined with other therapeutic agents. In this review, we will discuss the most recent findings in the mechanisms of action of CQ and HCQ in the immune system, and the use of these antimalarial drugs on diseases.</jats:p> </jats:sec>

Impact of the COVID-19 pandemic on patients with systemic lupus erythematosus: Observations from an Indian inception cohort

“…11,12 HCQ has many other mechanisms including change in lysosomal pH leading to reduced TLR signalling, decrease in pro-inflammatory cytokine release, induction of apoptosis, and inhibition of autophagy. 14 However, the clinical studies are conflicting in terms of the protective role of HCQ in the prevention of COVID-19. It has been shown that after high-risk or moderate-risk exposure to COVID-19, HCQ did not prevent illness when used as post-exposure prophylaxis.…”

“…13 So, hydroxychloroquine has both direct anti-viral effects and anti-inflammatory effects. 14 Various multi-centric clinical trials are being conducted to study the effect of this drug on prophylaxis as well as treatment of COVID-19. However, the evidence at present is not definitive regarding the role of HCQ.…”

Hydroxychloroquine use and progression or prognosis of COVID-19: a systematic review and meta-analysis

“…HCQ, as an aminoquinoline, has been extensively used for the prevention and therapy of malaria and rheumatic diseases (Martinez et al 2020). In the context of the COVID-19 pandemic and absence of effective drugs, HCQ has been approved for the treatment of hospitalized patients with COVID-19 on the grounds of anti-inflammatory and antiviral effects.…”

T Cell-Mediated Immune Responses to AAV and AAV Vectors

“…All of these drugs would impair primary T cell responses but may not block recall responses. Induction of CD4 + T cells could be inhibited by preventing antigen presentation through the MHC class II pathway through chloroquine, which prevents acidification of endosomes (118), cyclosporin A and tacrolimus, which both inhibit calcineurin (119) or blockers of the lysosomal protease cathepsin S, such as morpholinurea-leucine-homophenylalaninevinylsulfone-phenyl (120). Some of the drugs such as cyclosporin A and tacrolimus also block MHC class I antigen presentation, which can also be inhibited by proteasome inhibitors such as lactacystin (121) or inhibitors of TAP (122).…”