Evidence map›Paper›PMID 29516781›Full record

ArticleAmerican journal of physiology. Lung cellular and molecular physiology2018

Inhibiting Bruton's tyrosine kinase rescues mice from lethal influenza-induced acute lung injury.

Jon M Florence, Agnieszka Krupa, Laela M Booshehri, Sandra A Davis, Michael A Matthay, Anna K Kurdowska

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In one paragraph

Article in American journal of physiology. Lung cellular and molecular physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

66 citing papers in PubMed, 94 citations in OpenAlex.

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6 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 2 countries.

Jon M FlorenceCenter for Biomedical Research, University of Texas Health Science Center at Tyler , Tyler, Texas.
Agnieszka KrupaCenter for Biomedical Research, University of Texas Health Science Center at Tyler , Tyler, Texas.
Laela M BooshehriCenter for Biomedical Research, University of Texas Health Science Center at Tyler , Tyler, Texas.
Sandra A DavisCenter for Biomedical Research, University of Texas Health Science Center at Tyler , Tyler, Texas.
Michael A MatthayDepartment of Medicine and Anesthesia, Cardiovascular Research Institute, School of Medicine, University of California , San Francisco, California.
Anna K KurdowskaCenter for Biomedical Research, University of Texas Health Science Center at Tyler , Tyler, Texas.
The University of Texas Health Science Center at Tyler · USUniversity of California, San Francisco · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Infection with seasonal influenza A virus (IAV) leads to lung inflammation and respiratory failure, a main cause of death in influenza-infected patients. Previous experiments in our laboratory indicate that Bruton's tyrosine kinase (Btk) plays a substantial role in regulating inflammation in the respiratory region during acute lung injury in mice; therefore, we sought to determine if blocking Btk activity has a protective effect in the lung during influenza-induced inflammation. The Btk inhibitor ibrutinib (also known as PCI-32765) was administered intranasally to mice starting 72 h after lethal infection with IAV. Our data indicate that treatment with the Btk inhibitor not only reduced weight loss and led to survival, but also had a dramatic effect on morphological changes to the lungs, in IAV-infected mice. Attenuation of lung inflammation indicative of acute lung injury, such as alveolar hemorrhage, interstitial thickening, and the presence of alveolar exudate, together with reduced levels of the inflammatory mediators TNFα, IL-1β, IL-6, KC, and MCP-1, strongly suggests amelioration of the pathological immune response in the lungs to promote resolution of the infection. Finally, we observed that blocking Btk specifically in the alveolar compartment led to significant attenuation of neutrophil extracellular traps released into the lung in vivo and neutrophil extracellular trap formation in vitro. Our innovative findings suggest that Btk may be a new drug target for influenza-induced lung injury, and, in general, that immunomodulatory treatment may be key in treating lung dysfunction driven by excessive inflammation.

Indexed as

Acute Lung InjuryAdenineAgammaglobulinaemia Tyrosine KinaseAnimalsCytokinesExtracellular TrapsInfluenza A Virus, H1N1 SubtypeMacrophages, AlveolarMiceOrthomyxoviridae InfectionsPiperidinesProtein Kinase InhibitorsPyrazolesPyrimidinesAdenineAgammaglobulinaemia Tyrosine KinaseBtk protein, mouseCytokinesibrutinibPiperidinesProtein Kinase InhibitorsPyrazolesPyrimidinesacute lung injuryacute respiratory distress syndromeBruton’s tyrosine kinaseinfluenzaneutrophil

Identifiers

PMID29516781
PMCPMC6087894
OpenAlexW2794403789

What OpenQuestion holds

Textmetadata
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.