Evidence map›Paper›PMID 39284999›Full record

Trial reportLung2024

Effects of Azithromycin on Blood Inflammatory Gene Expression and Cytokine Production in Sarcoidosis.

Simon D Fraser, Susannah Thackray-Nocera, Caroline Wright, Rachel Flockton, Sally R James, Michael G Crooks, Paul M Kaye, Simon P Hart

Abstract readClinical Trial
In one paragraph

Trial report in Lung, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
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

8 authors.

Simon D FraserRespiratory Research Group, Hull York Medical School, Castle Hill Hospital, Cottingham, HU16 5JQ, UK.
Susannah Thackray-NoceraRespiratory Clinical Trials Unit, Hull University Teaching Hospitals NHS Trust, Castle Hill Hospital, Cottingham, HU16 5JQ, UK.
Caroline WrightRespiratory Clinical Trials Unit, Hull University Teaching Hospitals NHS Trust, Castle Hill Hospital, Cottingham, HU16 5JQ, UK.
Rachel FlocktonRespiratory Clinical Trials Unit, Hull University Teaching Hospitals NHS Trust, Castle Hill Hospital, Cottingham, HU16 5JQ, UK.
Sally R JamesBiosciences Technology Facility, Dept. of Biology, University of York, York, UK.
Michael G CrooksRespiratory Research Group, Hull York Medical School, Castle Hill Hospital, Cottingham, HU16 5JQ, UK.
Paul M KayeYork Biomedical Research Institute, University of York, York, YO10 5DD, UK.
Simon P HartRespiratory Research Group, Hull York Medical School, Castle Hill Hospital, Cottingham, HU16 5JQ, UK. s.hart@hull.ac.uk.

Funding

Wellcome TrustWellcome Trust WT104726
6 · The paper itself

Abstract

introductionIn sarcoidosis granulomas, monocyte-derived macrophages are activated by pro-inflammatory cytokines including TNF and IL-6. Current drug treatment for sarcoidosis aims to suppress inflammation but disabling side effects can ensue. The macrolide azithromycin may be anti-inflammatory. We aimed to determine whether treatment with azithromycin affects blood inflammatory gene expression and monocyte functions in sarcoidosis.

methodsBlood samples were collected from patients with chronic pulmonary sarcoidosis enrolled in a single arm, open label clinical trial who received oral azithromycin 250 mg once daily for 3 months. Whole blood inflammatory gene expression with or without LPS stimulation was measured using a 770-mRNA panel. Phenotypic analysis and cytokine production were conducted by flow cytometry and ELISA after 24h stimulation with growth factors and TLR ligands. mTOR activity was assessed by measuring phosphorylated S6RP.

resultsDifferential gene expression analysis indicated a state of heightened myeloid cell activation in sarcoidosis. Compared with controls, sarcoidosis patients showed increased LPS responses for several cytokines and chemokines. Treatment with azithromycin had minimal effect on blood gene expression overall, but supervised clustering analysis identified several chemokine genes that were upregulated. At the protein level, azithromycin treatment increased LPS-stimulated TNF and unstimulated IL-8 production. No other cytokines showed significant changes following azithromycin. Blood neutrophil counts fell during azithromycin treatment whereas mononuclear cells remained stable. Azithromycin had no detectable effects on mTOR activity or activation markers.

conclusionBlood myeloid cells are activated in sarcoidosis, but azithromycin therapy did not suppress inflammatory gene expression or cytokine production in blood.

trial registrationEudraCT 2019-000580-24 (17 May 2019).

Indexed as

AzithromycinCytokinesSarcoidosis, PulmonaryAdultAgedAnti-Inflammatory AgentsFemaleGene ExpressionHumansInflammation MediatorsInterleukin-8LipopolysaccharidesMaleMiddle AgedMonocytesTOR Serine-Threonine KinasesAnti-Inflammatory AgentsAzithromycinCXCL8 protein, humanCytokinesInflammation MediatorsInterleukin-8LipopolysaccharidesMTOR protein, humanTOR Serine-Threonine KinasesTumor Necrosis Factor-alphaCoughCytokinesInflammationInnate immunityMonocyteSarcoidosis

Identifiers

PMID39284999
PMCPMC11427505

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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 OpenQuestion graph.