Chloroquine Inhibits the Release of Inflammatory Cytokines by Human Lung Explants
Grassin-Delyle et al.,
Chloroquine Inhibits the Release of Inflammatory Cytokines by Human Lung Explants,
Clinical Infectious Diseases, doi:10.1093/cid/ciaa546 (Ex Vivo)
On human lung parenchymal explants, CQ concentration clinically achievable in the lung (100µM) inhibited the lipopolysaccharide-induced release of TNF-ɑ (by 76%), IL-6 (by 68%), CCL2 (by 72%), and CCL3 (by 67%). In addition to antiviral activity, CQ may also mitigate the cytokine storm associated with severe pneumonia caused by coronaviruses.
Grassin-Delyle et al., 8 May 2020, peer-reviewed, 8 authors.
Ex Vivo studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: Chloroquine inhibits the release of inflammatory cytokines
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Marion Brollo3, Emilie Catherinot1, Edouard Sage1,4, Louis-Jean Couderc1,3,
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Emmanuel Naline1,3, Philippe Devillier1,3
Department of Respiratory Diseases, Foch Hospital, Suresnes, France.
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INSERM Infection & inflammation, Département de Biotechnologie de la Santé, University Paris-
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Saclay, Montigny-le-Bretonneux, France.
Laboratory of Research in Respiratory Pharmacology, Exhalomics Facility, Foch Hospital, University
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Paris-Saclay, Suresnes, France.
UMR0892, INRAE, University Paris-Saclay, Jouy-en-Josas, France.
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Address correspondence to: Professor Philippe Devillier, Laboratory of Research in Respiratory
Pharmacology, Foch Hospital, University Paris-Saclay, 11 rue Guillaume Lenoir, F-92150 Suresnes,
France. Tel: (+33)146252791, Fax: (+33)140999657. E-mail: p.devillier@hopital-foch.org
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases
Society of America. All rights reserved. For permissions, e-mail:
journals.permissions@oup.com.
Stanislas Grassin-Delyle1,2, Hélène Salvator1,3,
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by human lung explants
Abstract
On human lung parenchymal explants, chloroquine concentration clinically achievable in the lung
(by 72%) and CCL3 (by 67%). Beside its antiviral activity, chloroquine might also mitigate the cytokine
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storm associated with severe pneumonia caused by coronaviruses.
Keywords: chloroquine; lung explant; tumour necrosis factor-alpha; interleukin-6;
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chemokine; lipopolysaccharide.
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(100 M) inhibited the lipopolysaccharide-induced release of TNF-by 76%), IL-6 (by 68%), CCL2
The severe pneumonia caused by severe acute respiratory syndrome coronaviruses (SARSCOVs) features rapid viral replication and then an intense, prolonged cytokine/chemokine response
cytokines, such as interleukin (IL)-6, tumour necrosis factor-alpha (TNF-α), macrophage
inflammatory protein-1α (CCL3), and monocyte chemoattractant protein 1 (CCL2) [1-4]. Reports that
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plasma cytokine levels are higher in patients requiring intensive care than those not requiring
intensive care, suggest that the cytokine storm is linked to disease severity [3]. Hence, dysregulated
and/or exaggerated cytokine and chemokine responses to SARS-CoV infection might have a major
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influence on the pathogenesis of coronavirus disease and the associated morbidity and mortality [1-
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4].
The antimalarial drugs chloroquine and hydroxychloroquine have been used to treat patients
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infected with SARS-CoV-2. Given the efficacy observed in trials conducted in China, chloroquine is to
be included in the forthcoming version of the Chinese national guidelines for the prevention,
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diagnosis, and treatment of pneumonia caused by SARS-CoV-2 [5]. Chloroquine will probably be the
first compound to be widely used in China and worldwide as the first-line treatment of severe SARS-
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CoV-2 infections due to its broad availability, low cost, and low frequency of adverse drug reactions
[6]. The Food and Drug Administration also encourages the use of chloroquine and
hydroxychloroquine..
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