The Effect of Glucocorticoids on Canine Lymphocyte Marker Expression and Apoptosis

Abstract

Background: Glucocorticoids are commonly administered to dogs for the treatment of inflammatory disorders, autoimmunity and cancers such as lymphoma. Despite evidence of clinical efficacy, understanding of the effects of glucocorticoids on cells of the canine immune system is limited.Hypothesis: Glucocorticoids affect the expression of phenotypic markers on canine lymphocytes and induce apoptosis. Animals: Fifteen healthy mixed breed dogs. Methods: Prospective randomized study. Prednisone was administered orally for 3 days, and cells aspirated from the popliteal lymph node before prednisone administration, and on days 1, 3, 10, 17, 24, and 38, were labeled with antibodies against canine CD3, CD4, CD8a, CD18, CD21, CD45, CD45RA, and CD90 molecules, and analyzed by flow cytometry. Additional samples were cultured in media with prednisolone for 24 hours and analyzed by cytometry for marker expression, and by gel electrophoresis for DNA fragmentation.Results: Treatment of dogs with glucocorticoids resulted in reduced (p # .05) proportions of CD3 (days 1, 3, 17, and 24), CD4 (days 3 and 10), CD21 (day 1, 3, and 38), CD45RA (day 17) and CD90 (days 1, 10, and 17) expressing lymphocytes, and reduced intensity of CD18 (day 17) and CD45 (day 17 and 24) molecules on nodal lymphocytes. Culture of lymphocytes with prednisolone for 24 hours caused a significant reduction in the expression of all markers (p # .05) and DNA fragmentation.Conclusions and Clinical Importance: Glucocorticoids significantly alter the expression of phenotypic markers on canine lymphocytes, and in vitro induce apoptosis. These findings identify potential mechanisms for clinical immunosuppression from glucocorticoid treatment.

A flow cytometric assessment of the lymphocyte immunophenotypes in dogs naturally infected with Babesia rossi

“…A significant decrease in the number of circulating B lymphocytes in dogs treated daily for 14 days with prednisone has been reported (127). In addition, immunosuppressive dosages of prednisone given to dogs for three consecutive days resulted in marked decreases in the percentage of lymph node CD21 + B lymphocytes at day 1, 3 and 38 after initiation of therapy (125). In our study we observed that Babesia-infected dogs that received glucocorticoids showed a significantly higher percentage circulating B lymphocytes at the time points post-presentation compared to Babesia-infected dogs that did not received glucocorticoid therapy.…”

“…In mice, infected with P. yoelii, lower numbers of effector CD8 + T lymphocytes were found to be mainly due to increased apoptosis rather than reduced recruitment or proliferation rates of naïve T lymphocytes (112). Similar In general, the effects of glucocorticoids on lymphocytes are variable and dependant on the glucocorticoid dose, as well as on the lymphoid subpopulation and activation state (125). In humans, the effect of glucocorticoids on B lymphocytes is characterised by a reduced proliferation of precursor B lymphocytes, whereas it results in increased production of certain antibody isotypes by mature plasma cells (126).…”

Marked hyperphosphatasemia associated with an acute leukemia in a Great Dane

“…Although steroid‐induced apoptosis is also reported for acute myeloid leukemia, it is less consistent . In addition, steroid sensitivity, resulting in increased apoptosis, has only been reported for canine lymphoid cells . Further canine studies are warranted to study these mechanisms.…”

Retrospective Study of Tick-Borne Pathogens and Observation of <i>Ehrlichia ewingii / Anaplasma phagocytophilum</i> and Hemotropic <i>Mycoplasma</i> spp. in Dogs’ Blood Films

“…Bacterial infections, among other infectious diseases are more important for left shift occurrence [72,73]. Glucocorticoids increase lymphocyte sequestration and apoptosis [74][75][76], some secreted cytokines in bacterial and viral infections also cause lymphopenia [77][78][79]. Reactive lymphocytes are antigen stimulated lymphocytes which their size and their cytoplasmic basophilia were increased [73].…”