ArticleThe Journal of clinical investigation2021
Tetracyclines improve experimental lymphatic filariasis pathology by disrupting interleukin-4 receptor-mediated lymphangiogenesis.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
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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
22 citing papers in PubMed, 34 citations in OpenAlex.
- The CCR2 inflammatory pathway is a target for improving severe disease and pulmonary inflammation in experimental COVID-19.Virulence · 2026Article
- Critical role of keratinocytes and protease-activated receptor 2 in secondary lymphedema development.Clinical and translational medicine · 2026Article
- Tetracycline Resistance Pattern Among Lymphatic Filariasis-Hyperendemic Communities in Southern Ghana: A Mixed-Method Approach.Health science reports · 2026Article
- Doxycycline: An essential tool for Alzheimer's disease.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Review
- Characteristics and advances in signaling pathways, cellular communication, cell junctions, and oxidative stress in lymphedema.Frontiers in cell and developmental biology · 2025Review
- Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce the risk of developing cancer-related lymphedema following axillary lymph node dissection (ALND).Frontiers in pharmacology · 2024Article
- Molecular pathophysiology of secondary lymphedema.Frontiers in cell and developmental biology · 2024Review
- Intestinal Lymphatic Dysfunction in Kidney Disease.Circulation research · 2023Review
- The role of macrophages in rosacea: implications for targeted therapies.Frontiers in immunology · 2023Review
- Imaging peripheral lymphatic dysfunction in chronic conditions.Frontiers in physiology · 2023Review
- The Role of Grass Compost andInternational journal of environmental research and public health · 2022Article
- A mouse infection model and long-term lymphatic endothelium co-culture system to evaluate drugs against adult Brugia malayi.PLoS neglected tropical diseases · 2022Article
- TGF-β1 mediates pathologic changes of secondary lymphedema by promoting fibrosis and inflammation.Clinical and translational medicine · 2022Article
- The Immunological Role of Vascular and Lymphatic Endothelial Cells in Filarial Infections.Animals : an open access journal from MDPI · 2022Review
- Doxycycline for the treatment of breast cancer-related lymphedema.Frontiers in pharmacology · 2022Article
- Pharmacological Treatment of Secondary Lymphedema.Frontiers in pharmacology · 2022Review
- The Relationship between VEGF-C, TAM, and Lymph Node Metastasis in Oral Cancer.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- NKp46Frontiers in immunology · 2022Article
- Eosinophils in filarial infections: Inducers of protection or pathology?Frontiers in immunology · 2022Review
- Pilot Study of Anti-Th2 Immunotherapy for the Treatment of Breast Cancer-Related Upper Extremity Lymphedema.Biology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Lymphatic filariasis is the major global cause of nonhereditary lymphedema. We demonstrate that the filarial nematode Brugia malayi induced lymphatic remodeling and impaired lymphatic drainage following parasitism of limb lymphatics in a mouse model. Lymphatic insufficiency was associated with elevated circulating lymphangiogenic mediators, including vascular endothelial growth factor C. Lymphatic insufficiency was dependent on type 2 adaptive immunity, the interleukin-4 receptor, and recruitment of C-C chemokine receptor-2-positive monocytes and alternatively activated macrophages with a prolymphangiogenic phenotype. Oral treatments with second-generation tetracyclines improved lymphatic function, while other classes of antibiotic had no significant effect. Second-generation tetracyclines directly targeted lymphatic endothelial cell proliferation and modified type 2 prolymphangiogenic macrophage development. Doxycycline treatment impeded monocyte recruitment, inhibited polarization of alternatively activated macrophages, and suppressed T cell adaptive immune responses following infection. Our results determine a mechanism of action for the antimorbidity effects of doxycycline in filariasis and support clinical evaluation of second-generation tetracyclines as affordable, safe therapeutics for lymphedemas of chronic inflammatory origin.
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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.