Evidence map›Paper›PMID 30646846›Full record

ArticleMolecular medicine (Cambridge, Mass.)2019

Btk inhibitor ibrutinib reduces inflammatory myeloid cell responses in the lung during murine pneumococcal pneumonia.

Alexander P de Porto, Zhe Liu, Regina de Beer, Sandrine Florquin, Onno J de Boer, Rudi W Hendriks, Tom van der Poll, Alex F de Vos

Open access · goldAbstract read
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
8.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 72 citations in OpenAlex.

  1. Review
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  5. Ibrutinib Delays ALS Installation and Increases Survival of SOD1Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 1 country.

Alexander P de PortoCenter for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room G2-132, 1105, AZ, Amsterdam, the Netherlands. a.p.deporto@amc.uva.nl.
Zhe LiuCenter for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room G2-132, 1105, AZ, Amsterdam, the Netherlands.
Regina de BeerCenter for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room G2-132, 1105, AZ, Amsterdam, the Netherlands.
Sandrine FlorquinDepartment of Pathology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Onno J de BoerDepartment of Pathology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Rudi W HendriksDepartment of Pulmonary Medicine, Erasmus MC Rotterdam, Rotterdam, The Netherlands.
Tom van der PollCenter for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room G2-132, 1105, AZ, Amsterdam, the Netherlands.
Alex F de VosCenter for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room G2-132, 1105, AZ, Amsterdam, the Netherlands.
Amsterdam University Medical Centers · NLUniversity of Amsterdam · NLAcademic Medical Center · NLErasmus University Rotterdam · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundStreptococcus pneumoniae is a major causative agent in community-acquired pneumonia and sepsis. Overwhelming lung inflammation during pneumococcal pneumonia may hamper lung function. Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (Btk), a key signaling protein controlling the activation of various immune cells, including macrophages and neutrophils. The aim of this study was to determine whether ibrutinib treatment ameliorates acute lung inflammation during pneumococcal pneumonia.

methodsMice were treated orally with ibrutinib and the effect on acute pulmonary inflammation elicited by the gram-positive bacterial cell wall component lipoteichoic acid (LTA) and during ceftriaxone-treated pneumococcal pneumonia was assessed.

resultsTreatment with ibrutinib prior to and after intranasal LTA instillation reduced alveolar macrophage activation, neutrophil influx, cytokine release and plasma leakage into the lung. Postponed treatment with ibrutinib supplementing antibiotic therapy during ongoing pneumococcal pneumonia did not impair bacterial killing in lung, blood and spleen. In this setting, ibrutinib reduced alveolar macrophage and systemic neutrophil activation and substantially diminished further monocyte and neutrophil influx in the lung. In vitro, ibrutinib inhibited macrophage TNF secretion and neutrophil activation upon LTA and pneumococcal stimulation.

conclusionsTaken together, these data indicate that the Btk inhibitor ibrutinib reduces inflammatory myeloid cell responses during acute pulmonary inflammation evoked by LTA and antibiotic-treated pneumococcal pneumonia and suggest that ibrutinib has the potential to inhibit ongoing lung inflammation in an acute infectious setting.

Indexed as

AdenineAgammaglobulinaemia Tyrosine KinaseAnimalsAnti-Bacterial AgentsAnti-Inflammatory AgentsBronchoalveolar Lavage FluidCeftriaxoneLipopolysaccharidesLungMaleMice, Inbred C57BLMice, KnockoutMyeloid CellsPiperidinesPneumonia, PneumococcalProtein Kinase InhibitorsAdenineAgammaglobulinaemia Tyrosine KinaseAnti-Bacterial AgentsAnti-Inflammatory AgentsBtk protein, mouseCeftriaxoneibrutinibLipopolysaccharideslipoteichoic acidPiperidinesProtein Kinase InhibitorsPyrazolesPyrimidinesTeichoic AcidsBruton’s tyrosine kinaseIbrutinibPneumoniaSepsisStreptococcus pneumoniae

Identifiers

PMID30646846
PMCPMC6332549
OpenAlexW2912634793

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.