In vivo effects of aspirin and cyclosporine on regulatory T cells and T-cell cytokine production in healthy dogs.
Vet Immunol Immunopathol
; 197: 63-68, 2018 Mar.
Article
de En
| MEDLINE
| ID: mdl-29475508
ABSTRACT
Cyclosporine and aspirin are routinely used in combination to treat immune-mediated hemolytic anemia (IMHA) in dogs. Cyclosporine is a potent immunosuppressive agent that targets T cell production of the cytokines IL-2 and IFN-γ. Low-dose aspirin is often used to inhibit platelet function in dogs with IMHA, since these animals are prone to life-threatening thromboembolic disease. In rodents and humans, aspirin and cyclosporine have both been shown to variably affect T cell cytokine production, and also numbers of circulating regulatory T cells (Tregs). In dogs, it has not yet been determined if concurrent aspirin alters the effects of cyclosporine on T-cell cytokine expression, or if either drug influences Treg numbers. In a crossover study, seven healthy young adult dogs were given either oral high-dose cyclosporine (10â¯mg/kg Q12â¯h), oral low-dose aspirin (1â¯mg/kg Q24â¯h), oral high-dose aspirin (10â¯mg/kg Q12â¯h), or combined low-dose aspirin with cyclosporine, each for 8â¯days, with a washout of at least 2 weeks after each treatment. Activated T cell cytokine expression (IL-2 & IFN-γ) and percent CD4â¯+â¯CD25â¯+â¯FOXP3+ Tregs were evaluated using flow cytometry, both prior to and on the last day of treatment. The difference between pre- and post-treatment values for each group, as well as the difference between treatment groups, was evaluated. Cyclosporine significantly decreased IL-2 and IFN-γ expression when used alone or in combination with low-dose aspirin. High-dose aspirin, but not low-dose aspirin, also significantly decreased IL-2 expression, although the decrease was not as marked as that seen with cyclosporine alone or in combination with aspirin. Neither low-dose nor high-dose aspirin significantly affected IFN-γ expression. No drug or drug combination affected Treg numbers. Low-dose aspirin given with cyclosporine creates the same degree of T-cell cytokine suppression as does cyclosporine alone, suggesting that the two drugs can be used concurrently without significantly altering the immunosuppressive mechanism of action of cyclosporine.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Acide acétylsalicylique
/
Interféron gamma
/
Interleukine-2
/
Ciclosporine
/
Lymphocytes T régulateurs
Limites:
Animals
Langue:
En
Journal:
Vet Immunol Immunopathol
Année:
2018
Type de document:
Article