Evidence map›Paper›PMID 40033742›Full record

ArticleInnate immunity

Preclinical development of the TLR4 antagonist FP12 as a drug lead targeting the HMGB1/MD-2/TLR4 axis in lethal influenza infection.

Kari Ann Shirey, Alessio Romerio, Mohammed Monsoor Shaik, David S Leake, Charys Palmer, Natalia Skupinska, Jules Paton, Grisha Pirianov, Jorge Cg Blanco, Stefanie N Vogel and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Innate immunity. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
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

11 authors.

Kari Ann ShireyDepartment of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, Maryland, USA.
Alessio RomerioDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milano, Italy.
Mohammed Monsoor ShaikDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milano, Italy.
David S LeakeSchool of Biological Sciences, Health and Life Sciences Building, University of Reading, Reading, Berkshire, UK.
Charys PalmerSchool of Life Sciences, Anglia Ruskin University, Cambridge, UK.
Natalia SkupinskaSchool of Life Sciences, Anglia Ruskin University, Cambridge, UK.
Jules PatonDepartment of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, Maryland, USA.ORCID 0009-0000-2242-251X
Grisha PirianovSchool of Life Sciences, Anglia Ruskin University, Cambridge, UK.
Jorge Cg BlancoSigmovir Biosystems Inc., Rockville, MD, USA.
Stefanie N VogelDepartment of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, Maryland, USA.
Francesco PeriDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milano, Italy.ORCID 0000-0002-3417-8224

Funding

QAQC Johns Hopkins Institute for Clinical and Translational ResearchUL1TR003098 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2019 to 2023
$57.7M
British Heart Foundation PG/20/10072NCATS NIH HHS UL1 TR003098
6 · The paper itself

Abstract

backgroundAcute Lung Injuries (ALI) are a severe consequence of influenza-induced cytokine storm that can cause respiratory failure and death. It has been demonstrated that Toll-like Receptor 4 (TLR4) is involved in cytokine storm and that TLR4

objectivesWe present here the preclinical development of FP12 as an anti-inflammatory lead compound acting on influenza-induced ALI.

methods

resultsFP12 treatment inhibited both LPS- and HMGB1-induced TLR4 intracellular pathways (MyD88 and TRIF) leading to significantly reduced levels of a variety of proinflammatory cytokines including Type I interferon (IFN-β), highlighting its effectiveness in controlling proinflammatory protein production and reducing inflammation. FP12 protected mice therapeutically from influenza virus-induced lethality and reduced both cytokine gene expression and High Mobility Group Box 1 (HMGB1) levels in the lungs as well as ALI.

conclusionFP12 can antagonize TLR4 activation in vitro and protects mice from severe influenza infection, most likely by reducing the TLR4-dependent cytokine storm mediated by danger-associated molecular patterns (DAMPs).

Indexed as

Acute Lung InjuryAnti-Inflammatory AgentsInfluenza, HumanLymphocyte Antigen 96Orthomyxoviridae InfectionsToll-Like Receptor 4AnimalsCell LineCytokinesHMGB1 ProteinHumansLipopolysaccharidesMiceMice, Inbred C57BLMice, KnockoutSignal TransductionAnti-Inflammatory AgentsCytokinesHMGB1 ProteinLipopolysaccharidesLymphocyte Antigen 96Tlr4 protein, mouseToll-Like Receptor 4ALIDrug discoveryHMGB1influenzaTLR4

Identifiers

PMID40033742
PMCPMC11877469

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.