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Tamoxifen reduces inflammatory infiltration of neutrophils in the airways

Agustín Mansilla, Jaime Soto, Claudio Henríquez, Amber Philp, Marcus A. Mall, José Sarmiento, Carlos A. Flores
doi: https://doi.org/10.1101/2020.06.19.161919
Agustín Mansilla
1Centro de Estudios Científicos (CECs), Valdivia. Chile
2Universidad Austral de Chile, Valdivia. Chile
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Jaime Soto
1Centro de Estudios Científicos (CECs), Valdivia. Chile
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Claudio Henríquez
3Instituto de Farmacología. Facultad de Ciencias Veterinarias. Universidad Austral de Chile. Valdivia, Chile
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Amber Philp
1Centro de Estudios Científicos (CECs), Valdivia. Chile
2Universidad Austral de Chile, Valdivia. Chile
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Marcus A. Mall
4Department of Pediatric Pulmonology, Immunology and Critical Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany
5Berlin Institute of Health (BIH), Berlin, Germany
6German Center for Lung Research (DZL), associated partner site, Berlin, Germany
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José Sarmiento
7Instituto de Fisiología. Facultad de Medicina. Universidad Austral de Chile. Valdivia, Chile
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Carlos A. Flores
1Centro de Estudios Científicos (CECs), Valdivia. Chile
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  • For correspondence: cflores@cecs.cl
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ABSTRACT

Tamoxifen is a drug of choice for treatment of breast cancer but it has also been reported to bear anti-inflammatory activity. Previously, we have observed that tamoxifen treatment successfully reduced inflammation in horses affected by equine asthma syndrome. More notorious, tamoxifen was effective at reducing the infiltration of neutrophils in the inflamed airways by a mechanism that increases efferocytosis, allowing the resolution of inflammation. Due to the emerging increase in patients with chronic inflammatory lung diseases, there is an urgent need for therapies that help reduce airway inflammation. Thus we tested the effect of tamoxifen on airway neutrophil infiltration by using three different mouse models for acute and chronic inflammation of the lung. We found that the drug was able to produce a significant reduction in neutrophils in all scenarios. Ussing chamber experiments demonstrated that tamoxifen has no effect on fluid secretion and absorption, discarding a possible reduction in mucociliary clearance due to the known ion-channel blocking effects of tamoxifen. Since this drug has been largely used in human medicine, tamoxifen might be a “low hanging fruit” for a novel anti-inflammatory therapy for airway diseases characterized by neutrophilic inflammation.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 20, 2020.
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Tamoxifen reduces inflammatory infiltration of neutrophils in the airways
Agustín Mansilla, Jaime Soto, Claudio Henríquez, Amber Philp, Marcus A. Mall, José Sarmiento, Carlos A. Flores
bioRxiv 2020.06.19.161919; doi: https://doi.org/10.1101/2020.06.19.161919
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Tamoxifen reduces inflammatory infiltration of neutrophils in the airways
Agustín Mansilla, Jaime Soto, Claudio Henríquez, Amber Philp, Marcus A. Mall, José Sarmiento, Carlos A. Flores
bioRxiv 2020.06.19.161919; doi: https://doi.org/10.1101/2020.06.19.161919

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