The effects of prolonged azathioprine administration on blood cells, lymphocytes and immunoglobulins of Iranian mixed-breed dogs

Background: Azathioprine is an immunosuppressive agent that is used in a variety of dermatologic, digestive and hematologic disorders in both humans and small animals. Aims: The effects of long term Azathioprine administration on complete blood count, rate of CD4+ and CD8+ lymphocytes, serum immunoglobulins and protein concentrations of mixed-breed dogs were evaluated in this study. Methods: 24 healthy mixed-breed dogs were divided randomly into two equal control and treatment groups. Dogs in the treatment group received the therapeutic dose of Azathioprine for four months, while the dogs in the control group didn't receive this drug. Peripheral blood samples were taken from both two groups before and after the trial to check CBC, CD4+ and CD8+ lymphocytes and the concentrations of total protein, albumin, serum IgM and IgG. Results: There was significant decrease in the levels of WBC, RBC, hematocrit and CD4 lymphocyte and double positive CD4/CD8 rates (all p values< 0.001), concentrations of total protein, albumin, serum IgG and IgM (P values: 0.014, 0.001, 0.007 and 0.041 respectively) in treatment group after the trial. Conclusions: Myelotoxicity induced by Azathioprine could be the probable cause of decrements in the rate of WBC and RBC. Decrease in the rate of dpCD4/CD8 might be due to decrement in dpCD4/CD8 progenitor cells and/or decrease in the activation rate of single positive T cells as the result of pharmacological effect of Azathioprine. Disrupted synthesis processes, from genes to proteins through Azathioprine might be the cause of decreases in the level of serum gamma globulins and protein.