Summary
Type 1 (insulin-dependent) diabetes mellitus results from autoimmune cell-mediated destruction of pancreatic islet Beta cells. Since theophylline has suppressive effects on immune responses, we sought to determine if this agent might protect against destruction of islet Beta cells in diabetes-prone BB rats. Diabetes-prone rats were divided into four groups and treated, from age 30 to 125 days, with: (a) no treatment (control), (b) theophylline 2 mg·.ml−1 added to the drinking water, (c) cyclosporine 5 mg·kg−1·day−1 administered by gavage, and (d) theophylline plus cyclosporine. By age 125 days, diabetes (glucosuria and serum glucose > 11mmol·.l−1) had appeared in 15 of 17 (88%) of control rats, 10 of 18 (56%) on theophylline, 6 of 17 (35%) on cyclosporine, and 1 of 17 (6%) on theophylline plus cyclosporine. Protection against diabetes by theophylline and cyclosporine was associated with preservation of pancreatic Beta cell mass (insulin content). The protective effects of combination therapy with theophylline and cyclosporine were achieved at very low serum concentrations of cyclosporine. These findings suggest that theophylline may be a useful adjunct in the immunosuppressive therapy of Type 1 diabetes.
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References
Mordes JP, Desemone J, Rossini AA (1987) The BB rat. Diab Metab Rev 3: 725–750
Coffey RG, Hadden JW (1985) Neurotransmitters, hormones, and cyclic nucleotides in lymphocyte regulation. Fed Proc 44: 112–117
Marni A, Ferrero ME, Rugarli C (1984) Effect of theophyllne in experimental pancreas allotransplantation in rats. Transplant Proc 16: 799–801
Ferrero E, Marni A, Ferrero MC, Gaya G, Rugarli C (1985) The effect of cyclosporine and aminophylline on streptozotocin-induced diabetes in rats. Immunol Let 10: 183–187
Secchi A, Crosti F, Pastore MR, Pavoni D, Falqui L, Navone P, Pontiroli AE, Ciboddo GF, Rugarli C, Pozza G (1988) In vivo and in vitro effects of theophylline administration in recent onset, type 1, diabetic patients. Diab Nutr Metab 1: 113–118
Bone AJ, Walker R, Varey AM, Cooke A, Baird JD (1990) Effect of cyclosporin on pancreatic events and development of diabetes in BB/Edinburgh rats. Diabetes 39: 508–514
Greiner DL, Mordes JP, Handler ES, Angelillo M, Nakamura N, Rossini AA (1987) Depletion of RT6.1+ T lymphocytes induces diabetes in resistant Biobreeding/Worcester (BB/W) rats. J Exp Med 166: 461–475
Didier M, Aussel C, Ferua B, Fehlmann M (1987) Regulation of interleukin 2 synthesis by cAMP in human T cells. J Immunol 139: 1179–1184
Wolberg G, Zimmerman TP, Hiemstra K, Winston M, Chu LC (1975) Adenosine inhibition of lymphocyte-mediated cytolysis; possible role of cyclic AMP. Science 187: 957–959
Katz P, Zaytoun AM, Fauci AS (1982) Mechanisms of human cell mediated cytotoxicity. I. Modulation of natural killer cell activity by cyclic nucleotides. J Immunol 129: 287–296
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Rabinovitch, A., Sumoski, W.L. Theophylline protects against diabetes in BB rats and potentiates cyclosporine protection. Diabetologia 33, 506–508 (1990). https://doi.org/10.1007/BF00405114
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DOI: https://doi.org/10.1007/BF00405114