Stanislas Grassin-Delyle, Hélène Salvator, Marion Brollo, Emilie Catherinot, Edouard Sage, Louis-Jean Couderc, Emmanuel Naline, Professor Philippe Devillier
doi:10.1093/cid/ciaa546/5831983
On human lung parenchymal explants, chloroquine concentration clinically achievable in the lung (100 M) inhibited the lipopolysaccharide-induced release of TNF-by 76%), IL-6 (by 68%), CCL2 (by 72%) and CCL3 (by 67%). Beside its antiviral activity, chloroquine might also mitigate the cytokine storm associated with severe pneumonia caused by coronaviruses.
A c c e p t e d M a n u s c r i p t 8 of 100 µM according to the lung-to-blood ratio in the pharmacokinetic model [12] . Hence, chloroquine treatment would preferably be initiated in the first days of lung symptoms caused by SARS-CoVs; first to reduce viral replication and then to mitigate the cytokine storm that typically occurs a few days later in last-stage disease. Given that chloroquine and hydroxychloroquine both appear to affect cytokine production by human monocytes and to accumulate in the lung in a similar way, they might exert the same effect on the cytokine storm [9, 12] . Although the in vitro effects on
References
-Buenestado, Chaumais, Grassin-Delyle, Risse, Naline et al., Roflumilast inhibits lipopolysaccharide-induced tumor necrosis factor-α and chemokine production by human lung parenchyma, PLoS One
-Devaux, Rolain, Colson, Raoult, New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?, International Journal of Antimicrobial Agents,
doi:10.1016/j.ijantimicag.2020.105938-Gao, Tian, Yang, Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies, Biosci Trends
-Mcchesney, Banks, Jr, Fabian, Tissue distribution of chloroquine, hydroxychloroquine, and desethylchloroquine in the rat, Toxicol Appl Pharmacol
-Mehta, Mcauley, Brown, Sanchez, Tattersall et al., HLH COVID-19: consider cytokine storm syndromes and immunosuppression, Lancet
-Mzayek, Deng, Mather, Wasilevich, Liu et al., Randomized dose-ranging controlled trial of AQ-13, a candidate
-Schrezenmeier, Dörner, Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology, Nat Rev Rheumatol
-Wang, Yang, Li, Wen, Zhang, Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China, Clin Infect Dis
-Yao, Ye, Zhang, Cui, Huang et al., In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Clin Infect Dis
Channappanavar, Perlman, Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology, Semin Immunopathol
Grassin-Delyle, Salvator, Mantov, Abrial, Brollo et al., Bitter Taste Receptors (TAS2Rs) in Human Lung Macrophages: Receptor Expression and Inhibitory Effects of TAS2R Agonists, Front Physiol
Huang, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet
Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res
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' <jats:p>On human lung parenchymal explants, chloroquine concentration '
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