Evidence mapPaperPMID 39294573Full record

ArticleMolecular medicine (Cambridge, Mass.)2024

Low-dose pro-resolving mediators temporally reset the resolution response to microbial inflammation.

Charles N Serhan, Nan Chiang, Robert Nshimiyimana

Abstract read
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

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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

3 authors.

Charles N SerhanDepartment of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Mass General Brigham and Harvard Medical School, 60 Fenwood Rd., Hale Building for Transformative Medicine 3-016, Boston, MA, 02115, USA. cserhan@bwh.harvard.edu.ORCID 0000-0003-4627-8545
Nan ChiangDepartment of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Mass General Brigham and Harvard Medical School, 60 Fenwood Rd., Hale Building for Transformative Medicine 3-016, Boston, MA, 02115, USA.ORCID 0000-0003-1963-1585
Robert NshimiyimanaDepartment of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Mass General Brigham and Harvard Medical School, 60 Fenwood Rd., Hale Building for Transformative Medicine 3-016, Boston, MA, 02115, USA.ORCID 0000-0003-0832-9938

Funding

Evaluating Resolution Mechanisms for Infectious InflammationR35GM139430 · BRIGHAM AND WOMEN'S HOSPITAL · 2025 to 2025
$746k
NIGMS NIH HHS R35 GM139430NIGMS NIH HHS R35GM139430
6 · The paper itself

Abstract

backgroundSpecialized pro-resolving mediators (SPMs) promote resolution of inflammation, clear infections and stimulate tissue regeneration. These include resolvins, protectins, and maresins. During self-resolving acute inflammation, SPMs are produced and have key functions activating endogenous resolution response for returning to homeostasis. Herein, we addressed whether infections initiated with ongoing inflammation alter resolution programs, and if low-dose repetitive SPM regimen re-programs the resolution response.

methodsInflammation was initiated with zymosan (1 mg/mouse) followed by E. coli (10

resultsE. coli infections initiated acute inflammation-resolution programs with temporal SPM production in the infectious exudates. Zymosan-induced inflammation prior to E. coli peritonitis shifted exudate resolution indices and delayed E. coli clearance. Lipid mediator metabololipidomics demonstrated that E. coli infection with ongoing zymosan-induced inflammation shifted the time course of exudate SPMs, activating a SPM cluster that included RvD1, RvD5 and MaR1 during the initiation phase of infectious inflammation (0-4 h); RvD5 and MaR1 were present also in the resolution phase (24-48 h). To emulate daily SPM regimens used in humans, a repetitive subthreshold dosing of the SPM panel RvD1, RvD2, RvD5, MaR1 and RvE2 each at 0.1 ng per mouse was administered. This low-dose SPM regimen accelerated exudate PMN clearance following zymosan-induced inflammation, and shortened the resolution interval by > 70%. These low-dose SPMs regulated genes and pathways related to immune response, chemokine clearance and tissue repair, as demonstrated by using RNA-sequencing.

conclusionsInfections encountered during ongoing inflammation in mice reset the resolution mechanisms of inflammation via SPM clusters. Low-dose SPMs activate innate immune responses and pathways towards the resolution response that can be reprogrammed.

Indexed as

Escherichia coli InfectionsInflammationPeritonitisAnimalsDisease Models, AnimalDocosahexaenoic AcidsEscherichia coliInflammation MediatorsMaleMiceMice, Inbred C57BLZymosanDocosahexaenoic AcidsInflammation MediatorsZymosanLC–MS–MSMacrophageMaresinsNeutrophilProtectinsResolvinsSPMs

Identifiers

PMID39294573
PMCPMC11411770

What Socratic holds

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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.