Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons.

Cell reports. Medicine (2020-12-31)
Nils Rother, Cansu Yanginlar, Rik G H Lindeboom, Siroon Bekkering, Mandy M T van Leent, Baranca Buijsers, Inge Jonkman, Mark de Graaf, Marijke Baltissen, Lieke A Lamers, Niels P Riksen, Zahi A Fayad, Willem J M Mulder, Luuk B Hilbrands, Leo A B Joosten, Mihai G Netea, Michiel Vermeulen, Johan van der Vlag, Raphaël Duivenvoorden

Hydroxychloroquine is being investigated for a potential prophylactic effect in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but its mechanism of action is poorly understood. Circulating leukocytes from the blood of coronavirus disease 2019 (COVID-19) patients show increased responses to Toll-like receptor ligands, suggestive of trained immunity. By analyzing interferon responses of peripheral blood mononuclear cells from healthy donors conditioned with heat-killed Candida, trained innate immunity can be modeled in vitro. In this model, hydroxychloroquine inhibits the responsiveness of these innate immune cells to virus-like stimuli and interferons. This is associated with a suppression of histone 3 lysine 27 acetylation and histone 3 lysine 4 trimethylation of inflammation-related genes, changes in the cellular lipidome, and decreased expression of interferon-stimulated genes. Our findings indicate that hydroxychloroquine inhibits trained immunity in vitro, which may not be beneficial for the antiviral innate immune response to SARS-CoV-2 infection in patients.

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Chloroquine diphosphate salt, powder or crystals, 98.5-101.0% (EP)
Ethylenediaminetetraacetic acid disodium salt dihydrate, suitable for electrophoresis, for molecular biology, 99.0-101.0% (titration)
Lipopolysaccharides from Escherichia coli O55:B5, γ-irradiated, BioXtra, suitable for cell culture
Hydroxychloroquine sulfate, ≥98% (HPLC), powder
cOmplete, EDTA-free Protease Inhibitor Cocktail, Tablets provided in EASYpacks