ArticleScientific reports2014
Azithromycin suppresses CD4(+) T-cell activation by direct modulation of mTOR activity.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Pooled it
- Trial
- "The effect of 48-weeks azithromycin therapy on levels of soluble biomarkers associated with HIV-associated chronic lung disease".International immunopharmacology · 2023Trial
- Azithromycin concentrations during long-term regimen, a pilot study in patients with MALT lymphoma.Scientific reports · 2021Trial
- Treatment of mucosa associated lymphoid tissue lymphoma with a long-term once-weekly regimen of oral azithromycin: Results from the phase II MALT-A trial.Hematological oncology · 2019Trial
- Severe Asthma Exacerbations: From Risk Factors to Precision Management Strategies.Journal of clinical medicine · 2026Review
- Lauric acid and microencapsulated zinc oxide have divergent effects on weaned pig growth performance, jejunal barrier function, and intestinal transcriptomic profiles.Journal of animal science · 2026Article
- Mass spectrometry-based serum peptidomic profiling reveals potential biomarker for canine hepatozoonosis.Scientific reports · 2025Article
- Immunity AgainstVaccines · 2025Article
- "Pleiotropic" Effects of Antibiotics: New Modulators in Human Diseases.Antibiotics (Basel, Switzerland) · 2024Review
- Immune modulatory effects of tulathromycin, gamithromycin, and oxytetracycline in cattle.BMC veterinary research · 2024Article
- The CD6 interactome orchestrates ligand-independent T cell inhibitory signaling.Cell communication and signaling : CCS · 2024Article
- Azithromycin targets the CD27 pathway to modulate CD27hi T-lymphocyte expansion and type-1 effector phenotype.Frontiers in immunology · 2024Article
- The Mechanism of Action and Clinical Efficacy of Low-Dose Long-Term Macrolide Therapy in Chronic Rhinosinusitis.International journal of molecular sciences · 2023Review
- Local Delivery of Azithromycin Nanoformulation Attenuated Acute Lung Injury in Mice.Molecules (Basel, Switzerland) · 2022Article
- Beneficial ex vivo immunomodulatory and clinical effects of clarithromycin in COVID-19.Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy · 2022Article
- Delivering macrolide antibiotics to heal a broken heart - And other inflammatory conditions.Advanced drug delivery reviews · 2022Review
- Current Status of the Spectrum and Therapeutics ofCancers · 2022Review
- Article
- Discovery of the first PD-1 ligand encoded by a pathogen.Frontiers in immunology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Advanced macrolides, such as azithromycin (AZM) or clarithromycin (CLM), are antibiotics with immunomodulatory properties. Here we have sought to evaluate their in vitro influence on the activation of CD4(+) T-cells. Isolated CD4(+) T-cells were stimulated with agonistic anti-CD3/anti-CD28 monoclonal antibodies in the presence of 0.6 mg/L, 2.5 mg/L, 10 mg/L or 40 mg/L AZM or CLM. Cell proliferation, cytokine level in supernatants and cell viability was assessed. Intracellular signaling pathways were evaluated using reporter cell lines, FACS analysis, immunoblotting and in vitro kinase assays. AZM inhibited cell proliferation rate and cytokine secretion of CD4(+) T-cells in a dose-dependent manner. Similarly, high concentrations of CLM (40 mg/L) also suppressed these T-cell functions. Analysis of molecular signaling pathways revealed that exposure to AZM reduced the phosphorylation of the S6 ribosomal protein, a downstream target of mTOR. This effect was also observed at 40 mg/L CLM. In vitro kinase studies using recombinant mTOR showed that AZM inhibited mTOR activity. In contrast to rapamycin, this inhibition was independent of FKBP12. We show for the first time that AZM and to a lesser extent CLM act as immunosuppressive agents on CD4(+) T-cells by inhibiting mTOR activity. Our results might have implications for the clinical use of macrolides.
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Registered trials
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.