Tamoxifen as a new therapeutic tool for neutrophilic lung inflammation.
Abstract: Neutrophilic asthma is an important disease subgroup, including patients with severe phenotypes and erratic responses to standard treatments. Tamoxifen (TX), a selective estrogen receptor modulator (SERM) used as treatment of human breast cancer, has been shown to induce early apoptosis of equine blood and bronchoalveolar lavage fluid (BALF) neutrophils in vitro. Equine recurrent airway obstruction (RAO) is a naturally occurring neutrophilic condition, closely related with human asthma. Our purpose was to investigate the therapeutic potential of tamoxifen in horses with neutrophilic lung inflammation. Methods: Twelve horses underwent acute lung inflammation through exposure to allergens known to cause RAO, after which they received treatment with either tamoxifen or dexamethasone. Outcome measures included evaluation of clinical signs, BALF cytology, and early apoptosis of blood and BALF neutrophils. Results: Tamoxifen treatment decreased BALF neutrophil counts (65.3 ± 19.38% before treatment; 7.6 ± 4.5% 2 days post-treatment,; and 13.6 ± 9.3% 5 days post-treatment). A similar decrease was observed with dexamethasone treatment (48.6 ± 5.88% before treatment; 11.5 ± 8.1% 2 days post-treatment; 14.6 ± 10.3% 5 days post-treatment). Clinical and endoscopic scores improved in both treatment groups. Tamoxifen treatment significantly increased early apoptosis of peripheral blood neutrophils at 5 days post-treatment (27.04 ± 15.2%), and in BALF neutrophils at 2 and 5 days post-treatment (42.11 ± 11.67% and 48.98 ± 2.6%, respectively). Conclusions: Tamoxifen treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood and BALF neutrophils, reduction in BALF neutrophils and improvement in the animals' clinical status.
© 2015 Asian Pacific Society of Respirology.
Publication Date: 2015-10-29 PubMed ID: 26510482DOI: 10.1111/resp.12664Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article discusses how tamoxifen (TX), often used to treat breast cancer, could present new therapeutic possibilities for neutrophilic lung inflammation, a condition related to severe forms of asthma. The treatment results of TX were compared with results using dexamethasone, a commonly used anti-inflammatory medication, in horses affected by similar lung conditions.
Methodology
- 12 horses underwent acute lung inflammation that was induced by exposure to allergens known to cause Recurrent Airway Obstruction (RAO).
- These horses were then treated with either tamoxifen or dexamethasone to compare the efficacy of these treatments.
- Outcome measures included the evaluation of clinical signs, bronchoalveolar lavage fluid (BALF) cytology, and early apoptosis of blood and BALF neutrophils.
Results
- Tamoxifen treatment resulted in a considerable decrease in BALF neutrophil counts.
- Notably, dexamethasone treatment also resulted in a similar reduction in BALF neutrophil counts.
- The clinical and endoscopic scores showed significant improvements in horses from both treatment groups.
- Tamoxifen was also distinguished for promoting early apoptosis, or programmed cell death of peripheral blood neutrophils, and in BALF neutrophils at two and five days post-treatment.
Conclusion
- The study concluded that tamoxifen could play a therapeutic role in conditions like acute pulmonary inflammation.
- Among the observed benefits of tamoxifen treatment included the promotion of early apoptosis of blood and BALF neutrophils, a reduction in BALF neutrophils, and an overall improvement in the clinical status of the horses tested.
Consequently, the study suggests that more research could be done to explore the application of tamoxifen as a possible treatment for severe asthma in humans.
Cite This Article
APA
Perez B, Henriquez C, Sarmiento J, Morales N, Folch H, Galesio JS, Uberti B, Morán G.
(2015).
Tamoxifen as a new therapeutic tool for neutrophilic lung inflammation.
Respirology, 21(1), 112-118.
https://doi.org/10.1111/resp.12664 Publication
Researcher Affiliations
- Department of Pharmacology, Austral University of Chile, Valdivia, Chile.
- Graduate School, Austral University of Chile, Valdivia, Chile.
- Department of Pharmacology, Austral University of Chile, Valdivia, Chile.
- Department of Physiology, Austral University of Chile, Valdivia, Chile.
- Department of Pharmacology, Austral University of Chile, Valdivia, Chile.
- Department of Immunology, Faculty of Medicine, Austral University of Chile, Valdivia, Chile.
- Department of Clinical Science, Faculty of Veterinary Science, Austral University of Chile, Valdivia, Chile.
- Department of Clinical Science, Faculty of Veterinary Science, Austral University of Chile, Valdivia, Chile.
- Department of Pharmacology, Austral University of Chile, Valdivia, Chile.
MeSH Terms
- Airway Obstruction / drug therapy
- Airway Obstruction / immunology
- Airway Obstruction / pathology
- Allergens / immunology
- Animals
- Anti-Inflammatory Agents / pharmacology
- Apoptosis / drug effects
- Apoptosis / immunology
- Asthma / drug therapy
- Asthma / immunology
- Asthma / pathology
- Bronchoalveolar Lavage Fluid / immunology
- Dexamethasone / pharmacology
- Disease Models, Animal
- Horses
- Humans
- Neutrophils / immunology
- Pneumonia / drug therapy
- Pneumonia / immunology
- Pneumonia / pathology
- Selective Estrogen Receptor Modulators / pharmacology
- Tamoxifen / pharmacology
Citations
This article has been cited 16 times.- Salinas C, Barriga K, Albornoz A, Alarcon P, Quiroga J, Uberti B, Sarmiento J, Henriquez C, Ehrenfeld P, Burgos RA, Moran G. Tamoxifen triggers the in vitro release of neutrophil extracellular traps in healthy horses. Front Vet Sci 2022;9:1025249.
- Wu YS, Chen CR, Yeh YT, Lin HH, Peng YH, Lin YL. 7,7″-Dimethoxyagastisflavone Inhibits Proinflammatory Cytokine Release and Inflammatory Cell Recruitment through Modulating ERα Signaling. Biomedicines 2021 Nov 26;9(12).
- Zhang YM. Orosomucoid-like protein 3, rhinovirus and asthma. World J Crit Care Med 2021 Sep 9;10(5):170-182.
- Davis KU, Sheats MK. The Role of Neutrophils in the Pathophysiology of Asthma in Humans and Horses. Inflammation 2021 Apr;44(2):450-465.
- Filep JG, Ariel A. Neutrophil heterogeneity and fate in inflamed tissues: implications for the resolution of inflammation. Am J Physiol Cell Physiol 2020 Sep 1;319(3):C510-C532.
- Albornoz A, Morales N, Uberti B, Henriquez C, Burgos RA, Alarcon P, Moran G. Tamoxifen and its metabolites induce mitochondrial membrane depolarization and caspase-3 activation in equine neutrophils. Vet Med Sci 2020 Nov;6(4):673-678.
- Maghsoudloo M, Azimzadeh Jamalkandi S, Najafi A, Masoudi-Nejad A. Identification of biomarkers in common chronic lung diseases by co-expression networks and drug-target interactions analysis. Mol Med 2020 Jan 17;26(1):9.
- Gajardo G, López-Muñoz R, Plaza A, Uberti B, Sarmiento J, Morán G, Henríquez C. Tamoxifen in horses: pharmacokinetics and safety study. Ir Vet J 2019;72:5.
- Polari L, Anttila S, Helenius T, Wiklund A, Linnanen T, Toivola DM, Määttä J. Novel Selective Estrogen Receptor Modulator Ameliorates Murine Colitis. Int J Mol Sci 2019 Jun 20;20(12).
- Morales N, Henriquez C, Sarmiento J, Uberti B, Moran G. Tamoxifen inhibits chemokinesis in equine neutrophils. Ir Vet J 2018;71:22.
- Mainguy-Seers S, Picotte K, Lavoie JP. Efficacy of tamoxifen for the treatment of severe equine asthma. J Vet Intern Med 2018 Sep;32(5):1748-1753.
- Leffler J, Stumbles PA, Strickland DH. Immunological Processes Driving IgE Sensitisation and Disease Development in Males and Females. Int J Mol Sci 2018 May 23;19(6).
- Olave C, Morales N, Uberti B, Henriquez C, Sarmiento J, Ortloff A, Folch H, Moran G. Tamoxifen induces apoptotic neutrophil efferocytosis in horses. Vet Res Commun 2018 Mar;42(1):57-63.
- Albornoz A, Morales B, Fernandez VB, Henriquez C, Quiroga J, Alarcón P, Moran G, Burgos RA. Obesity-Associated Metabolomic and Functional Reprogramming in Neutrophils from Horses with Asthma. Animals (Basel) 2025 Jul 7;15(13).
- Gutiérrez-Brito JA, Lomelí-Nieto JÁ, Muñoz-Valle JF, Oregon-Romero E, Corona-Angeles JA, Hernández-Bello J. Sex hormones and allergies: exploring the gender differences in immune responses. Front Allergy 2024;5:1483919.
- Rodríguez M, Quiroga J, Cortés B, Morán G, Henríquez C. Effects of tamoxifen on the immune response phenotype in equine peripheral blood mononuclear cells. Front Vet Sci 2024;11:1381162.
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