Evidence map›Paper›PMID 41503141›Full record

ArticleDiscovery immunology2025

Fluoroquinolones directly drive mitochondrial hyperpolarization and modulate iNOS expression in monocyte-derived macrophage populations.

Alexander W Hardgrave, Megan Dooley, Ivy Maminimini, Adura Faniyi, Antonia Christodoulidou, Yasmine Alshammari, Helen J March, Riccardo V D'Elia, John J Worthington

Abstract read
In one paragraph

Article in Discovery immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Alexander W HardgraveFaculty of Health and Medicine, Department of Biomedical and Life Sciences, University of Lancaster, Lancaster, UK.
Megan DooleyFaculty of Health and Medicine, Department of Biomedical and Life Sciences, University of Lancaster, Lancaster, UK.
Ivy MaminiminiFaculty of Health and Medicine, Department of Biomedical and Life Sciences, University of Lancaster, Lancaster, UK.
Adura FaniyiFaculty of Health and Medicine, Department of Biomedical and Life Sciences, University of Lancaster, Lancaster, UK.
Antonia ChristodoulidouFaculty of Health and Medicine, Department of Biomedical and Life Sciences, University of Lancaster, Lancaster, UK.
Yasmine AlshammariFaculty of Health and Medicine, Department of Biomedical and Life Sciences, University of Lancaster, Lancaster, UK.
Helen J MarchPharmacy Department, Royal Oldham Hospital, Northern Care Alliance NHS Trust, Oldham, UK.
Riccardo V D'EliaCBR Division, Defence Science and Technology Laboratory Porton Down, Salisbury, UK.
John J WorthingtonFaculty of Health and Medicine, Department of Biomedical and Life Sciences, University of Lancaster, Lancaster, UK.ORCID https://orcid.org/0000-0002-1429-5669

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: The fluoroquinolone levofloxacin is often selected for use prophylactically as well as during respiratory infections. However, studies on how these antibiotics may alter innate immunity, as opposed to their bactericidal activity, are limited. Materials & Methods: We employed a murine model of therapeutically relevant antibiotic dosing to investigate the effect of prophylactic levofloxacin treatment on innate immunity. Results: We observed mild pathology at the barrier sites of both the lung and colon in terms of alveolar space and goblet cell numbers, respectively. Although we saw no alteration in lung immune populations of neutrophils, eosinophils, or dendritic cells, we did see heightened expression of macrophage inducible nitric oxide synthase (iNOS). Interestingly this was only present in the shorter-lived CD206- interstitial macrophage subset and not observed in the long-lived resident alveolar population. Within the large intestine levofloxacin also targeted iNOS expression in the shorter-lived TIM4-CD4+ population but conversely inhibiting expression in the microbially rich colon. We therefore utilized the bone marrow-derived macrophage system, devoid of microbial interactions and demonstrated that levofloxacin had a direct effect on driving iNOS expression and increasing phagocytosis but only when present in developing macrophages and not mature macrophage populations. Our macrophage observations were replicated in ciprofloxacin, but not doxycycline-treated animals, indicating a fluoroquinolone specific action. Mechanistically, fluoroquinolone treatment was associated with mitochondrial hyperpolarization, indicating a direct alteration of macrophage immunity via off target effects. Conclusion: Collectively, this study demonstrates a direct action of fluoroquinolones on macrophage immunity, which should be considered when selecting antibiotics for tissue specific and prophylactic use.

Indexed as

antibioticslungmacrophagemitochondriamucosal immunology

Identifiers

PMID41503141
PMCPMC12770987

What Socratic holds

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LicenceCC BY
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Registered trials

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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.