Tamoxifen as a new therapeutic tool for neutrophilic lung inflammation.
OBJECTIVE
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.
Department of Pharmacology, Austral University of Chile, Valdivia, Chile.|Graduate School, Austral University of Chile, Valdivia, Chile.
Barbara
B
Perez
Department of Pharmacology, Austral University of Chile, Valdivia, Chile.
Claudio
C
Henriquez
Department of Physiology, Austral University of Chile, Valdivia, Chile.
Jose
J
Sarmiento
Department of Pharmacology, Austral University of Chile, Valdivia, Chile.
Natalia
N
Morales
Department of Immunology, Faculty of Medicine, Austral University of Chile, Valdivia, Chile.
Hugo
H
Folch
Department of Clinical Science, Faculty of Veterinary Science, Austral University of Chile, Valdivia, Chile.
Juan S
JS
Galesio
Department of Clinical Science, Faculty of Veterinary Science, Austral University of Chile, Valdivia, Chile.
Benjamin
B
Uberti
Department of Pharmacology, Austral University of Chile, Valdivia, Chile.
Gabriel
G
Morán
D000402:Airway Obstruction / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D000485:Allergens / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D006736:Horses; D006801:Humans; D009504:Neutrophils / Q000276:immunology*; D011014:Pneumonia / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology*
D000485:Allergens; D000893:Anti-Inflammatory Agents; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D003907:Dexamethasone
early apoptosis; equine recurrent airway obstruction; neutrophil; neutrophilic asthma; tamoxifen