Evidence map›Paper›PMID 25839777›Full record

ArticleInflammatory bowel diseases2015

Killing of Escherichia coli by Crohn's Disease Monocyte-derived Macrophages and Its Enhancement by Hydroxychloroquine and Vitamin D.

Paul K Flanagan, Direkrit Chiewchengchol, Helen L Wright, Steven W Edwards, Abdullah Alswied, Jack Satsangi, Sreedhar Subramanian, Jonathan M Rhodes, Barry J Campbell

Open access · bronzeAbstract read
In one paragraph

Article in Inflammatory bowel diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.7field-weighted citation impact, top 14% 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

12 citing papers in PubMed, 25 citations in OpenAlex.

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  11. Replication of Crohn's Disease MucosalPathogens (Basel, Switzerland) · 2019
    Article
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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

9 authors at 3 institutions in 2 countries.

Paul K Flanagan*Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; †Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom; ‡Immunology Unit and Center of Excellence in Immunology and Immune-mediated Disease, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; §Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Edinburgh, Scotland; and ‖Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, United Kingdom.
Direkrit Chiewchengchol
Helen L Wright
Steven W Edwards
Abdullah Alswied
Jack Satsangi
Sreedhar Subramanian
Jonathan M Rhodes
Barry J Campbell
University of Liverpool · GBChulalongkorn University · THRoyal Liverpool University Hospital · GB

Funding

Arthritis Research UK 19437Chief Scientist Office CZB/4/540Chief Scientist Office ETM/137Chief Scientist Office ETM/75Department of Health BRF-2011-025Medical Research Council G0600329Medical Research Council G0800675Medical Research Council G0800759Wellcome Trust
6 · The paper itself

Abstract

backgroundCrohn's disease (CD) is associated with defective innate immunity, including impaired neutrophil chemotaxis, and mucosal invasion by bacteria, particularly adherent and invasive Escherichia coli that replicate inside macrophage phagolysosomes. We compared CD and healthy control (HC) macrophages for their abilities to kill E. coli and generate neutrophil chemoattractants and also assessed the effects of hydroxychloroquine (HCQ) and vitamin D on killing of phagocytosed E. coli.

methodsPeripheral blood monocyte-derived macrophages from CD and HC were compared for bacterial killing and generation of neutrophil chemoattractants in response to CD-derived E. coli. Escherichia coli replication was also assessed in the presence and absence of HCQ, alone and with antibiotics, and vitamin D.

resultsMonocyte-derived macrophages from patients with CD were similar to HC in allowing replication of phagocytosed CD-derived E. coli: HM605 {CD: N = 10, mean fold replication in 3 hr = 1.08 (95% confidence interval [CI], 0.39-1.78); HC: N = 9, 1.50 (95% CI, 1.02-1.97); P = 0.15} and also in generation of neutrophil chemoattractants in response to E. coli (mean fold chemotaxis relative to control: CD = 2.55 [95% CI, 2.31-2.80]; HC = 2.65 [95% CI, 2.46-2.85], P = 0.42). HCQ and 1,25 OH2-vitamin D3 both caused dose-dependent inhibition of intramacrophage E. coli replication 3-hour postinfection; HCQ: 73.9% inhibition (P < 0.001) at 1 μg/mL, accompanied by raised intraphagosomal pH, and 1,25 OH2-vitamin D3: 80.7% inhibition (P < 0.05) at 80 nM. HCQ had synergistic effects with doxycycline and ciprofloxacin.

conclusionsCD and HC macrophages perform similarly in allowing replication of phagocytosed E. coli and generating neutrophil chemoattractants. Replication of phagocytosed E. coli was substantially decreased by HCQ and vitamin D. These warrant further therapeutic trials in CD in combination with relevant antibiotics.

Indexed as

Immunity, InnateAdultAnimalsCells, CulturedCrohn DiseaseCytokinesDrug Therapy, CombinationEnzyme InhibitorsEscherichia coliEscherichia coli InfectionsFemaleHumansHydroxychloroquineIntestinal MucosaMacrophagesMaleCytokinesEnzyme InhibitorsHydroxychloroquineVitamin DVitamins

Identifiers

PMID25839777
PMCPMC4894789
OpenAlexW2047634639

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.