ArticleEBioMedicine2016
Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response to Pulmonary Tuberculosis in a Rabbit Model.
Article in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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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
57 citing papers in PubMed, 77 citations in OpenAlex.
- DRTB-HDT: a randomized controlled trial of two adjunctive host-directed therapies in rifampin-resistant tuberculosis.BMC infectious diseases · 2025Trial
- Adjunctive host-directed therapies for pulmonary tuberculosis: a prospective, open-label, phase 2, randomised controlled trial.The Lancet. Respiratory medicine · 2021Trial
- The study of immunological markers in tuberculosis across animal models and its translation to human research.Lab animal · 2026Review
- Dovramilast for Erythema Nodosum Leprosum in Patients With Leprosy in Nepal: Protocol for a Phase 2 Open-Label Pilot Study.JMIR research protocols · 2026Article
- Structural and biochemical insights into the inhibition ofRSC chemical biology · 2026Article
- Post-TB lung disease: pathogenesis, host-directed therapies, and the C3HeB/FeJ model for pre-clinical advances.Infection and immunity · 2026Review
- Genome-wide transcriptional landscape ofFrontiers in immunology · 2026Article
- Host-directed therapeutics against antimicrobial-resistant bacterial infections: emerging roles of multi-omics and systems biology.Frontiers in pharmacology · 2026Review
- Host-directed therapy for tuberculosis.European journal of medical research · 2025Review
- Review
- Microenvironments of tuberculous granuloma: advances and opportunities for therapy.Frontiers in immunology · 2025Review
- Mathematical modeling suggests heterogeneous replication of Mycobacterium tuberculosis in rabbits.PLoS computational biology · 2024Article
- A Review of Antibacterial Candidates with New Modes of Action.ACS infectious diseases · 2024Review
- Mathematical modeling suggests heterogeneous replication ofbioRxiv : the preprint server for biology · 2024Article
- Immune Responses toBiomedicines · 2024Article
- Article
- Host Cell Death and Modulation of Immune Response againstInternational journal of molecular sciences · 2024Review
- Potential of Neuroinflammation-Modulating Strategies in Tuberculous Meningitis: Targeting Microglia.Aging and disease · 2024Review
- Article
- Effect of IL-17A on the immune response to pulmonary tuberculosis induced by high- and low-virulence strains of Mycobacterium bovis.PloS one · 2024Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
objectivesAdjunctive host-directed therapy is emerging as a new potential approach to improve the outcome of conventional antimicrobial treatment for tuberculosis (TB). We tested the ability of a phosphodiesterase-4 inhibitor (PDE4i) CC-11050, co-administered with the first-line anti-TB drug isoniazid (INH), to accelerate bacillary killing and reduce chronic inflammation in the lungs of rabbits with experimental Mycobacterium tuberculosis (Mtb) infection.
methodsA rabbit model of pulmonary TB that recapitulates the pathologic manifestations seen in humans was used. Rabbits were infected with virulent Mtb by aerosol exposure and treated for eight weeks with INH with or without CC-11050, starting at four weeks post infection. The effect of CC-11050 treatment on disease severity, pathology, bacillary load, T cell proliferation and global lung transcriptome profiles were analyzed.
resultsSignificant improvement in bacillary clearance and reduced lung pathology and fibrosis were noted in the rabbits treated for eight weeks with INH + CC-11050, compared to those treated with INH or CC-11050 only. In addition, expression of host genes associated with tissue remodeling, tumor necrosis factor alpha (TNF-α) regulation, macrophage activation and lung inflammation networks was dampened in CC-11050-treated, compared to the untreated rabbits.
conclusionsAdjunctive CC-11050 therapy significantly improves the response of rabbits with experimental pulmonary TB to INH treatment. We propose that CC-11050 may be a promising candidate for host directed therapy of patients with pulmonary TB, reducing the duration and improving clinical outcome of antibiotic treatment.
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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.