Hydroxychloroquine inhibits IL-1β production from amyloid-stimulated human neutrophils

Fujita, Yuya; Matsuoka, Naoki; Temmoku, Jumpei; Furuya, Makiko Yashiro; Asano, Tomohiko; Sato, Shuzo; Kobayashi, Hiroko; Watanabe, Hiroshi; Suzuki, Eiji; Urano, Takeshi; Kozuru, Hideko; Yatsuhashi, Hiroshi; Koga, Tomohiro; Kawakami, Atsushi; Migita, Kiyoshi

doi:10.1186/s13075-019-2040-6

Cited by 22 publications

(15 citation statements)

References 28 publications

(30 reference statements)

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“…These in vitro data suggest that 24 hour in vitro treatment with HCQ minimally impacts immune gene transcription and support findings that HCQ has potential immunomodulatory and lipid metabolism effects [11]. Specifically, previous work from in vivo studies has reported that HCQ treatment significantly decreased serum TNF-A and increased IL-10 levels in women following treatment with 400mg/per day orally [12] and inhibited IL-1β production from stimulated human neutrophils [13]. In the context of COVID-19 infection, clinical reports indicate severe patients exhibit a well-known immune cytokine storm that leads to multi-organ failure [14,15].…”

Section: Treatment Of Resting Peripheral Blood Mononuclear Cells Withsupporting

confidence: 79%

Comparativein vitrotranscriptomic analyses of COVID-19 candidate therapy hydroxychloroquine suggest limited immunomodulatory evidence of SARS-CoV-2 host response genes

Corley

Sugai

Schotsaert

et al. 2020

Preprint

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Hydroxychloroquine (HCQ) has emerged as a potential and controversial antiviral candidate therapy for COVID-19. While many clinical trials are underway to test the efficacy of HCQ as a treatment for COVID-19, underlying mechanisms of HCQ in the setting of COVID-19 remain unclear. Hence, we examined differential gene expression signatures of HCQ exposure, in vitro SARS-CoV-2 infection, and host signatures of COVID-19 in blood, bronchoalveolar lavage, and postmortem lung to evaluate whether HCQ transcriptome signatures associate with restoration of SARS-CoV-2-related host transcriptional responses. Here, we show that 24 hours of in vitro treatment of peripheral blood mononuclear cells(PBMC) with HCQ significantly impacted transcription of 16 genes involved in immune regulation and lipid metabolism. Using transcriptome data from in vitro SARS-CoV-2 infected NHBE and A549 cells and PBMC derived from confirmed COVID-19 infected patients, we determined that only 0.24% of the COVID-19 PBMC differentially expressed gene set and 0.39% of the in vitro SARS-CoV-2 cells differentially expressed gene set overlapped with HCQ-related differentially expressed genes. Moreover, we observed that HCQ treatment significantly impacted transcription of 159 genes in human primary monocyte-derived macrophages involved in cholesterol biosynthetic process and chemokine activity. Notably, when we compared the macrophage HCQ-related gene lists with genes transcriptionally altered during SARS-CoV-2 infection and in bronchoalveolar lavage of COVID-19+ patients, the CXCL6 gene was impacted in all three transcriptional signatures revealing evidence in favor of chemokine modulation. HCQrelated transcriptional changes minimally overlapped with host genes altered in postmortem lung biopsies from COVID-19 participants. These results may provide insight into the immunomodulation mechanisms of HCQ treatment in the setting of COVID-19 and suggest HCQ is not a panacea to SARS-CoV-2 infection.was not certified by peer review)

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Section: Treatment Of Resting Peripheral Blood Mononuclear Cells Withsupporting

confidence: 79%

Comparativein vitrotranscriptomic analyses of COVID-19 candidate therapy hydroxychloroquine suggest limited immunomodulatory evidence of SARS-CoV-2 host response genes

Corley

Sugai

Schotsaert

et al. 2020

Preprint

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“…Hydroxychloroquine and azithromycin were reported as effective anti-SARS-CoV-2 agents ( Ohe et al, 2020 ; Zhou D. et al, 2020 ). Fujita et al demonstrated that hydroxychloroquine significantly inhibited IL-1β production in activated human neutrophils in vitro ( Fujita et al, 2019 ). Hydroxychloroquine inhibited NET formation and ameliorated the hypercoagulation state in mice with orthotopic pancreatic adenocarcinoma.…”

Section: Drugs Targeting Neutrophils For Covid-19 Associated Ardsmentioning

confidence: 99%

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

et al. 2020

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This review describes targeting neutrophils as a potential therapeutic strategy for acute respiratory distress syndrome (ARDS) associated with coronavirus disease 2019 (COVID-19), a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutrophil counts are significantly elevated in patients with COVID-19 and significantly correlated with disease severity. The neutrophil-to-lymphocyte ratio can serve as a clinical marker for predicting fatal complications related to ARDS in patients with COVID-19. Neutrophil-associated inflammation plays a critical pathogenic role in ARDS. The effector functions of neutrophils, acting as respiratory burst oxidants, granule proteases, and neutrophil extracellular traps, are linked to the pathogenesis of ARDS. Hence, neutrophils can not only be used as pathogenic markers but also as candidate drug targets for COVID-19 associated ARDS.

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“…Treatment with hydroxychloroquine was associated with impaired IL-1β production in SAA-stimulated human neutrophils without affecting the initial activation process of NLRP3 inflammasome, such as pro-IL-1β induction or NLRP3 induction. These findings suggest that hydroxychloroquine affects the activation process of NLRP3, and reduces the production of IL-1β in human neutrophils as the innate immune cells (Fujita et al 2019).…”

Section: The Effect Of Cq and Hcq On Nlrp3 Inflammasome Activationmentioning

confidence: 74%

Chloroquine/hydroxychloroquine: an inflammasome inhibitor in severe COVID-19?

Bahadoram

Keikhaei

Saeedi-Boroujeni

et al. 2021

Naunyn-Schmiedeberg's Arch Pharmacol

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Chloroquine and hydroxychloroquine belong to the aminoquinoline drugs. Studies revealed that chloroquine and hydroxychloroquine shows antagonism activity against COVID-19 under laboratory conditions. ARDS and ALI are conditions that occur in patients with COVID-19 as the main pathological complications of cytokine storm. Inflammasomes play a key role in the pathogenesis of many diseases associated with destructive inflammation. NLRP3 inflammasome has been shown to play a key role in the pathogenesis of viral diseases. The possible role of NLRP3 inflammasome inhibitors in the treatment of COVID-19 has been considered. We surveyed the potential inhibitory effect of chloroquine and hydroxychloroquine on inflammasome. Studies indicate that one of the possible anti-inflammatory mechanisms of chloroquine and hydroxychloroquine is inhibition of the activity of NLRP3 inflammasome.

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Hydroxychloroquine inhibits IL-1β production from amyloid-stimulated human neutrophils

Cited by 22 publications

References 28 publications

Comparativein vitrotranscriptomic analyses of COVID-19 candidate therapy hydroxychloroquine suggest limited immunomodulatory evidence of SARS-CoV-2 host response genes

Comparativein vitrotranscriptomic analyses of COVID-19 candidate therapy hydroxychloroquine suggest limited immunomodulatory evidence of SARS-CoV-2 host response genes

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

Chloroquine/hydroxychloroquine: an inflammasome inhibitor in severe COVID-19?

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