Plasma concentration of injectable contraceptive correlates with reduced cervicovaginal growth factor expression in South African women.
Adult
Biomarkers
Cervix Uteri
/ drug effects
Chromatography, Liquid
Contraceptive Agents, Female
/ administration & dosage
Cytokines
/ biosynthesis
Drug Monitoring
Female
Gene Expression Regulation
/ drug effects
Humans
Intercellular Signaling Peptides and Proteins
/ genetics
Microbiota
Mucous Membrane
/ immunology
South Africa
Tandem Mass Spectrometry
Vagina
/ drug effects
Young Adult
Journal
Mucosal immunology
ISSN: 1935-3456
Titre abrégé: Mucosal Immunol
Pays: United States
ID NLM: 101299742
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
19
06
2019
accepted:
15
12
2019
revised:
10
11
2019
pubmed:
4
1
2020
medline:
11
5
2021
entrez:
4
1
2020
Statut:
ppublish
Résumé
Long-acting injectable contraceptives have been associated with mucosal immune changes and increased HIV acquisition, but studies have often been hampered by the inaccuracy of self-reported data, unknown timing of injection, and interactions with mucosal transmission co-factors. We used mass spectrometry to quantify the plasma concentrations of injectable contraceptives in women from the CAPRISA004 study (n = 664), with parallel quantification of 48 cytokines and >500 host proteins in cervicovaginal lavage. Higher DMPA levels were associated with reduced CVL concentrations of GCSF, MCSF, IL-16, CTACK, LIF, IL-1α, and SCGF-β in adjusted linear mixed models. Dose-dependent relationships between DMPA concentration and genital cytokines were frequently observed. Unsupervised clustering of host proteins by DMPA concentration suggest that women with low DMPA had increases in proteins associated with mucosal fluid function, growth factors, and keratinization. Although DMPA was not broadly pro-inflammatory, DMPA was associated with increased IP-10 in HSV-2 seropositive and older women. DMPA-cytokine associations frequently differed by vaginal microbiome; in non-Lactobacillus-dominant women, DMPA was associated with elevated IL-8, MCP-1, and IP-10 concentrations. These data confirm a direct, concentration-dependant effect of DMPA on functionally important immune factors within the vaginal compartment. The biological effects of DMPA may vary depending on age, HSV-2 status, and vaginal microbiome composition.
Identifiants
pubmed: 31896762
doi: 10.1038/s41385-019-0249-y
pii: S1933-0219(22)00310-5
doi:
Substances chimiques
Biomarkers
0
Contraceptive Agents, Female
0
Cytokines
0
Intercellular Signaling Peptides and Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
449-459Subventions
Organisme : CIHR
ID : TMI 138658
Pays : Canada
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