cAMP and ATP levels in rat peripheral blood lymphocytes in low-dose streptozotocin-treated rats: Effect of pharmacological immunomodulation

M. E. Ferrero, A. Marni, E. Ferrero

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Similar autoimmune mechanisms have been proposed in the pathogenesis of human type 1 insulin-dependent diabetes and in that of diabetes induced in mice by multiple low doses of streptozotocin (STZ). The experimental murine model of diabetes and the model of spontaneous immune insulitis in BB rats have been useful to study a possible etiologic relation with the human supposed autoimmune diabetes. Differences have been noted in mouse strain susceptibility to multiple STZ treatments, and in susceptible strains influences of background, sex, and thymus were shown. Many investigations have supported the hypothesis that diabetes induction by subdiabetogenic doses of STZ in mice may involve T-cell-dependent autoimmune mechanisms, and a cell-mediated anti-beta-cell autoimmunity has been cited as important in beta-cell destruction. In human type 1 diabetes an immunosuppressive therapeutic treatment with cyclosporine (CsA) has been used with the aim of regulating the immune cellular response of the patients. To clarify the role of immunological factors in the induction of experimental diabetes by multiple low doses of STZ, we previously studied the activity of two immunosuppressant drugs in STZ-treated rats. In male Wistar STZ-treated rats, CsA administration favored and aminophylline (APH) treatment protected against the induction of diabetes. Concomitant treatment with CsA and APH was not not effective in protecting rats from the diabetogenic effect of STZ. We supposed that CsA may act by enhancing the direct beta-cytotoxic activity of STZ. However, to interpret the importance of immunological factors in the pathogenetic mechanism of diabetes by low doses of STZ, and possibly to compare the results to those obtained in human insulin-dependent diabetes mellitus, we evaluated lymphocyte function in this diabetic experimental model. Since several lymphocyte immunological functions seem to be related to cAMP intracellular content, and since we demonstrated some significant modifications in lymphocytic cAMP and ATP levels induced by continuous treatment in rats with CsA or APH, we studied the modifications induced by STZ and concomitant treatments with APH and/or CsA on intralymphocytic cAMP levels. We also evaluated intralymphocytic ATP levels in the same experimental conditions. It was hoped that the study would clarify the role of lymphocytes in diabetes induction by multiple subdiabetogenic doses of STZ.

Original languageEnglish
Pages (from-to)1528-1531
Number of pages4
JournalTransplantation Proceedings
Issue number6
Publication statusPublished - 1986

ASJC Scopus subject areas

  • Surgery
  • Transplantation


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