Evidence map›Paper›PMID 30452655›Full record

ArticleThe Journal of infectious diseases2019

The Injectable Contraceptive Medroxyprogesterone Acetate Attenuates Mycobacterium tuberculosis-Specific Host Immunity Through the Glucocorticoid Receptor.

Michele Tomasicchio, Malika Davids, Anil Pooran, Grant Theron, Liezel Smith, Lynn Semple, Richard Meldau, Janet Patricia Hapgood, Keertan Dheda

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 33% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

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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 3 countries.

Michele TomasicchioCentre for Lung Infection and Immunity, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town.
Malika DavidsCentre for Lung Infection and Immunity, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town.
Anil PooranCentre for Lung Infection and Immunity, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town.
Grant TheronCentre for Lung Infection and Immunity, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town.
Liezel SmithCentre for Lung Infection and Immunity, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town.
Lynn SempleCentre for Lung Infection and Immunity, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town.
Richard MeldauCentre for Lung Infection and Immunity, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town.
Janet Patricia HapgoodDepartment of Molecular and Cell Biology, University of Cape Town, South Africa.
Keertan DhedaCentre for Lung Infection and Immunity, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town.
University of Cape Town · ZALung Institute · USLondon School of Hygiene & Tropical Medicine · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe effects of the widely used progestin-only injectable contraceptives, medroxyprogesterone acetate (MPA) and norethisterone acetate (NET-A), on host susceptibility to Mycobacterium tuberculosis (Mtb) are unknown.

methodsWe recruited human immunodeficiency virus-uninfected females, not taking any contraceptives, from Cape Town, South Africa, to evaluate the effect of MPA, NET-A, and dexamethasone on Mtb containment in monocyte-derived macrophages co-incubated with purified protein derivative (PPD)-driven peripheral blood-derived effector cells.

resultsMPA (P < .005) and dexamethasone (P < .01), but not NET-A, significantly attenuated Mtb containment in Mtb-infected macrophages co-cultured with PPD-driven effector cells at physiologically relevant concentrations and in a dose-dependent manner. Antagonizing the glucocorticoid receptor with mifepristone (RU486) abrogated the reduction in Mtb containment. In PPD-stimulated peripheral blood mononuclear cells, MPA and dexamethasone, but not NET-A, upregulated (median [interquartile range]) regulatory T cells (5.3% [3.1%-18.2%]; P < .05), reduced CD4+ T-cell interferon-γ (21% [0.5%-28%]; P < .05) and granzyme B production (12.6% [7%-13.5%]; P < .05), and reduced CD8+ perforin activity (2.2% [0.1%-7%]; P < .05). RU486 reversed regulatory T-cell up-regulation and the inhibitory effect on Th1 and granzyme/perforin-related pathways.

conclusionsMPA, but not NET-A, subverts mycobacterial containment in vitro and downregulates pathways associated with protective CD8+- and CD4+-related host immunity via the glucocorticoid receptor. These data potentially inform the selection and use of injectable contraceptives in tuberculosis-endemic countries.

Indexed as

Contraceptive Agents, FemaleDexamethasoneDisease SusceptibilityDose-Response Relationship, DrugFemaleFlow CytometryHumansImmunityImmunity, CellularMedroxyprogesterone AcetateMycobacterium tuberculosisNorethindrone AcetateReceptors, GlucocorticoidT-Lymphocytes, RegulatoryTuberculosis, PulmonaryContraceptive Agents, FemaleDexamethasoneMedroxyprogesterone AcetateNorethindrone AcetateReceptors, Glucocorticoidinjectable contraceptivemedroxyprogesterone acetatenorethisteronepathogenesistuberculosis

Identifiers

PMID30452655
PMCPMC6452311
OpenAlexW2901675381

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.