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
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