Abstract
Chloroquine (CQ) and hydroxychloroquine (HCQ) are derivatives of 4-aminoquinoline compounds with over 60 years of safe clinical usage. CQ and HCQ are able to inhibit the production of cytokines such as interleukin- (IL-) 1, IL-2, IL-6, IL-17, and IL-22. Also, CQ and HCQ inhibit the production of interferon- (IFN-) α and IFN-γ and/or tumor necrotizing factor- (TNF-) α. Furthermore, CQ blocks the production of prostaglandins (PGs) in the intact cell by inhibiting substrate accessibility of arachidonic acid necessary for the production of PGs. Moreover, CQ affects the stability between T-helper cell (Th) 1 and Th2 cytokine secretion by augmenting IL-10 production in peripheral blood mononuclear cells (PBMCs). Additionally, CQ is capable of blocking lipopolysaccharide- (LPS-) triggered stimulation of extracellular signal-modulated extracellular signal-regulated kinases 1/2 in human PBMCs. HCQ at clinical levels effectively blocks CpG-triggered class-switched memory B-cells from differentiating into plasmablasts as well as producing IgG. Also, HCQ inhibits cytokine generation from all the B-cell subsets. IgM memory B-cells exhibits the utmost cytokine production. Nevertheless, CQ triggers the production of reactive oxygen species. A rare, but serious, side effect of CQ or HCQ in nondiabetic patients is hypoglycaemia. Thus, in critically ill patients, CQ and HCQ are most likely to deplete all the energy stores of the body leaving the patient very weak and sicker. We advocate that, during clinical usage of CQ and HCQ in critically ill patients, it is very essential to strengthen the CQ or HCQ with glucose infusion. CQ and HCQ are thus potential inhibitors of the COVID-19 cytokine storm.
Highlights
Chloroquine (CQ) and hydroxychloroquine (HCQ) are derivatives of 4-aminoquinoline compounds with over 60 years of safe clinical use in the treatment of malaria and, recently, the treatment of inflammatory disorders [1, 2]
CQ was capable of inhibiting toll-like receptors (TLRs)-7 downregulatory signaling pathways resulting in the blockade of transcription factors like interferon regulatory factor- (IRF-) 7, which modulates the production of IFN-α, an effective CD8 T-cell immune stimulator [20,21,22]
This study further revealed that the blockade of IL-1β production stimulated by weak-base amines occurred via the inhibition of pro-IL-1β rather than via reduced IL-1β mRNA [30]
Summary
Chloroquine (CQ) and hydroxychloroquine (HCQ) are derivatives of 4-aminoquinoline compounds with over 60 years of safe clinical use in the treatment of malaria and, recently, the treatment of inflammatory disorders [1, 2]. In recent years, CQ and HCQ have gained special attention because of the nonexistence of effective and efficient antiviral medications against new emerging viruses such as human immunodeficiency virus (HIV), dengue virus, chikungunya virus, and Ebola virus [4,5,6]. These compounds are readily available, cost effective, highly tolerated by the body, and elicit very critical immunomodulatory activities [4]. Most of the articles reviewed were indexed in PubMed with strict inclusion criteria being in vitro and in vivo up- or downregulation of these immune and inflammatory biomarkers in different disease conditions
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