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. 1999 Jan;63(1):18–24.

The effects of prednisone and azathioprine on circulating immunoglobulin levels and lymphocyte subpopulations in normal dogs.

N E Rinkardt 1, S A Kruth 1, A Kaushik 1
PMCID: PMC1189510  PMID: 9918329

Abstract

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.

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Selected References

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  1. Abdou N. I., Zweiman B., Casella S. R. Effects of azathioprine therapy on bone marrow-dependent and thymus-dependent cells in man. Clin Exp Immunol. 1973 Jan;13(1):55–64. [PMC free article] [PubMed] [Google Scholar]
  2. Beale K. M. Azathioprine for treatment of immune-mediated diseases of dogs and cats. J Am Vet Med Assoc. 1988 May 1;192(9):1316–1318. [PubMed] [Google Scholar]
  3. Boumpas D. T., Chrousos G. P., Wilder R. L., Cupps T. R., Balow J. E. Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann Intern Med. 1993 Dec 15;119(12):1198–1208. doi: 10.7326/0003-4819-119-12-199312150-00007. [DOI] [PubMed] [Google Scholar]
  4. Butler W. T., Rossen R. D. Effects of corticosteroids on immunity in man. I. Decreased serum IgG concentration caused by 3 or 5 days of high doses of methylprednisolone. J Clin Invest. 1973 Oct;52(10):2629–2640. doi: 10.1172/JCI107455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cobbold S., Metcalfe S. Monoclonal antibodies that define canine homologues of human CD antigens: summary of the First International Canine Leukocyte Antigen Workshop (CLAW). Tissue Antigens. 1994 Mar;43(3):137–154. doi: 10.1111/j.1399-0039.1994.tb02315.x. [DOI] [PubMed] [Google Scholar]
  6. De Paoli P., Villalta D., Battistin S., Gasparollo A., Santini G. Selective loss of OKT8 lymphocytes on density gradient centrifugation separation of blood mononuclear cells. J Immunol Methods. 1983 Jul 15;61(2):259–260. doi: 10.1016/0022-1759(83)90170-9. [DOI] [PubMed] [Google Scholar]
  7. FAHEY J. L., ROBINSON A. G. FACTORS CONTROLLING SERUM GAMMA-GLOBULIN CONCENTRATION. J Exp Med. 1963 Nov 1;118:845–868. doi: 10.1084/jem.118.5.845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fujisawa K., Tani P., Piro L., McMillan R. The effect of therapy on platelet-associated autoantibody in chronic immune thrombocytopenic purpura. Blood. 1993 Jun 1;81(11):2872–2877. [PubMed] [Google Scholar]
  9. Gorman N. T., Werner L. L. Immune-mediated diseases of the dog and cat. IV. Therapy and immunodiagnosis. Br Vet J. 1986 Nov-Dec;142(6):498–505. doi: 10.1016/0007-1935(86)90106-5. [DOI] [PubMed] [Google Scholar]
  10. Guenther W., Schumm M., Buettner M., Voss C., Kremmer E., Thierfelder S., Wilmanns W., Kolb H. J. NK activity of canine blood and marrow cells. Tissue Antigens. 1994 Mar;43(3):198–201. doi: 10.1111/j.1399-0039.1994.tb02323.x. [DOI] [PubMed] [Google Scholar]
  11. Houston D. M., Taylor J. A. Acute pancreatitis and bone marrow suppression in a dog given azathioprine. Can Vet J. 1991 Aug;32(8):496–497. [PMC free article] [PubMed] [Google Scholar]
  12. Kristensen F., Kristensen B., Lazáry S. The lymphocyte stimulation test in veterinary immunology. Vet Immunol Immunopathol. 1982 Jan;3(1-2):203–277. doi: 10.1016/0165-2427(82)90036-8. [DOI] [PubMed] [Google Scholar]
  13. Lanza L., Scudeletti M., Puppo F., Bosco O., Peirano L., Filaci G., Fecarotta E., Vidali G., Indiveri F. Prednisone increases apoptosis in in vitro activated human peripheral blood T lymphocytes. Clin Exp Immunol. 1996 Mar;103(3):482–490. doi: 10.1111/j.1365-2249.1996.tb08306.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Levy J., Barnett E. V., MacDonald N. S., Klinenberg J. R., Pearson C. M. The effect of azathioprine on gammaglobulin synthesis in man. J Clin Invest. 1972 Sep;51(9):2233–2238. doi: 10.1172/JCI107031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Matus R. E., Gordon B. R., Leifer C. E., Saal S., Hurvitz A. I. Plasmapheresis in five dogs with systemic immune-mediated disease. J Am Vet Med Assoc. 1985 Sep 15;187(6):595–599. [PubMed] [Google Scholar]
  16. Miller E. Immunosuppressive therapy in the treatment of immune-mediated disease. J Vet Intern Med. 1992 Jul-Aug;6(4):206–213. doi: 10.1111/j.1939-1676.1992.tb00340.x. [DOI] [PubMed] [Google Scholar]
  17. Moore P. F., Rossitto P. V., Danilenko D. M., Wielenga J. J., Raff R. F., Severns E. Monoclonal antibodies specific for canine CD4 and CD8 define functional T-lymphocyte subsets and high-density expression of CD4 by canine neutrophils. Tissue Antigens. 1992 Aug;40(2):75–85. doi: 10.1111/j.1399-0039.1992.tb01963.x. [DOI] [PubMed] [Google Scholar]
  18. Moriello K. A., Bowen D., Meyer D. J. Acute pancreatitis in two dogs given azathioprine and prednisone. J Am Vet Med Assoc. 1987 Sep 15;191(6):695–696. [PubMed] [Google Scholar]
  19. Ogilvie G. K., Felsburg P. J., Harris C. W. Short-term effect of cyclophosphamide and azathioprine on selected aspects of the canine blastogenic response. Vet Immunol Immunopathol. 1988 Mar;18(2):119–127. doi: 10.1016/0165-2427(88)90054-2. [DOI] [PubMed] [Google Scholar]
  20. Paliogianni F., Ahuja S. S., Balow J. P., Balow J. E., Boumpas D. T. Novel mechanism for inhibition of human T cells by glucocorticoids. Glucocorticoids inhibit signal transduction through IL-2 receptor. J Immunol. 1993 Oct 15;151(8):4081–4089. [PubMed] [Google Scholar]
  21. Renzi P., Ginns L. C. Analysis of T cell subsets in normal adults. Comparison of whole blood lysis technique to Ficoll-Hypaque separation by flow cytometry. J Immunol Methods. 1987 Apr 2;98(1):53–56. doi: 10.1016/0022-1759(87)90434-0. [DOI] [PubMed] [Google Scholar]
  22. Rinkardt N. E., Kruth S. A. Azathioprine-induced bone marrow toxicity in four dogs. Can Vet J. 1996 Oct;37(10):612–613. [PMC free article] [PubMed] [Google Scholar]
  23. Rivas A. L., Kimball E. S., Quimby F. W., Gebhard D. Functional and phenotypic analysis of in vitro stimulated canine peripheral blood mononuclear cells. Vet Immunol Immunopathol. 1995 Mar;45(1-2):55–71. doi: 10.1016/0165-2427(94)05330-u. [DOI] [PubMed] [Google Scholar]
  24. Rivas A. L., Kimball E. S., Quimby F. W., Gebhard D. Functional and phenotypic analysis of in vitro stimulated canine peripheral blood mononuclear cells. Vet Immunol Immunopathol. 1995 Mar;45(1-2):55–71. doi: 10.1016/0165-2427(94)05330-u. [DOI] [PubMed] [Google Scholar]
  25. SELL S. EVIDENCE FOR SPECIES' DIFFERENCES IN THE EFFECT OF SERUM GAMMA-GLOBULIN CONCENTRATION ON GAMMA-GLOBULIN CATABOLISM. J Exp Med. 1964 Nov 1;120:967–986. doi: 10.1084/jem.120.5.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Vitale M., Papa S., Mariani A. R., Facchini A., Rizzoli R., Manzoli F. A. Use of poligonal windows for physical discrimination among mononuclear subpopulations in flow cytometry. J Immunol Methods. 1987 Jan 26;96(1):63–68. doi: 10.1016/0022-1759(87)90368-1. [DOI] [PubMed] [Google Scholar]
  27. WALDMANN T. A., SCHWAB P. J. IGG (7 S GAMMA GLOBULIN) METABOLISM IN HYPOGAMMAGLOBULINEMIA: STUDIES IN PATIENTS WITH DEFECTIVE GAMMA GLOBULIN SYNTHESIS, GASTROINTESTINAL PROTEIN LOSS, OR BOTH. J Clin Invest. 1965 Sep;44:1523–1533. doi: 10.1172/JCI105259. [DOI] [PMC free article] [PubMed] [Google Scholar]

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