Rinkardt N E, Kruth S A, Kaushik A
Department of Clinical Studies, University of Guelph, Ontario.
Can J Vet Res. 1999 Jan;63(1):18-24.
This study investigates serum immunoglobulin (SIg) levels and lymphocyte subpopulations in normal dogs in response to putative immunosuppressive doses of prednisone and/or azathioprine. The objectives were to quantify SIg levels and lymphocyte subpopulations, including Thy-1+, CD4+, CD8+ and B cells, in normal dogs both before and after the administration of prednisone and/or azathioprine at 2 mg/kg, PO, each. Eighteen beagles were divided into 3 groups of 6 dogs each. Blood samples for radial immunodiffusion assay of IgG, IgM and IgA, complete blood count (CBC)and flow cytometry were collected prior to the administration of any drugs and again after 14 d of azathioprine, prednisone or azathioprine and prednisone. Peripheral blood mononuclear cells were isolated using density centrifugation and were incubated with monoclonal antibodies reacting with CD4+, CD8+, Thy-1+ and membrane immunoglobulin. Lymphocyte subsets were quantified using flow cytometry. Azathioprine-treated dogs had no significant changes in SIg levels or lymphocyte subpopulations. Prednisone-treated dogs had significant (P < 0.05) decreases in all SIg levels, all lymphocyte subpopulations and erythrocyte numbers, and had an increase in neutrophil counts. Prednisone and azathioprine-treated dogs had significant (P < 0.05) decreases in serum IgG levels and Thy-1+ and CD8+ lymphocyte subpopulations, with an increase in the CD4:CD8. These dogs also had a significant decrease in erythrocyte number and a significant increase in the monocyte count. These findings suggest that azathioprine and prednisone in combination or prednisone alone may be useful for the treatment of T cell-mediated diseases since decreased circulating T cell levels were demonstrated following treatment. The combination of drugs or azathioprine alone may not be appropriate for treatment of acute or autoantibody-mediated immune disease, because SIg levels were minimally affected by treatment.
本研究调查正常犬在给予假定免疫抑制剂量的泼尼松和/或硫唑嘌呤后血清免疫球蛋白(SIg)水平及淋巴细胞亚群的变化。目的是量化正常犬在分别口服2mg/kg泼尼松和/或硫唑嘌呤前后的SIg水平及淋巴细胞亚群,包括Thy-1⁺、CD4⁺、CD8⁺和B细胞。18只比格犬被分为3组,每组6只。在给予任何药物之前以及在给予硫唑嘌呤、泼尼松或硫唑嘌呤与泼尼松联合用药14天后,采集血样用于IgG、IgM和IgA的单向免疫扩散测定、全血细胞计数(CBC)及流式细胞术检测。采用密度离心法分离外周血单核细胞,并与与CD4⁺、CD8⁺、Thy-1⁺和膜免疫球蛋白反应的单克隆抗体孵育。使用流式细胞术对淋巴细胞亚群进行定量分析。硫唑嘌呤治疗的犬SIg水平和淋巴细胞亚群无显著变化。泼尼松治疗的犬所有SIg水平、所有淋巴细胞亚群及红细胞数量均显著降低(P<0.05),中性粒细胞计数增加。泼尼松和硫唑嘌呤联合治疗的犬血清IgG水平、Thy-1⁺和CD8⁺淋巴细胞亚群显著降低(P<0.05),CD4:CD8升高。这些犬的红细胞数量也显著减少,单核细胞计数显著增加。这些发现表明,由于治疗后循环T细胞水平降低,硫唑嘌呤与泼尼松联合或单独使用泼尼松可能对治疗T细胞介导的疾病有用。药物联合或单独使用硫唑嘌呤可能不适用于治疗急性或自身抗体介导的免疫疾病,因为治疗对SIg水平影响极小。