Synergistic effect of deoxyspergualin (DSP) and cyclosporin A (CsA) in the prevention of spontaneous autoimmune diabetes in BB rats

R. Di Marco, P. Zaccone, G. Magro, S. Grasso, M. Lunetta, W. Barcellini, V. M. Nicolosi, P. L. Meroni, F. Nicoletti

Research output: Contribution to journalArticlepeer-review

Abstract

Dose-dependent side effects are frequently observed with immunosuppressive drugs of potential relevance for the immunotherapy of insulin-dependent diabetes mellitus (IDDM), such as CsA and DSP. If CsA and DSP acted synergistically in vivo, their combined use would allow using each compound at lower doses than those required when each drug is given in monotherapy. Consequently, dose-dependent side effects could be reduced and the therapeutic activity maintained or even enforced. Toward this end we studied the effects of combined treatment with CsA and DSP on the course of IDDM in the diabetes-prone (DP)-BB rat. The results show that two 'low' doses of CsA (2 mg/kg) and DSP(1 mg/kg) that are clinically ineffective in suppressing IDDM development in BE rats when administered alone under a prolonged prophylactic regimen (30-105 days old), may successfully prevent, but not cure, the disease when given contemperaneously under the same experimental conditions. The combined treatment was well tolerated, and no side effects were noticed. These data suggest that the combined use of CsA and DSP may deserve consideration for its possible application in the prevention/treatment of human IDDM and other autoimmune diseases.

Original languageEnglish
Pages (from-to)338-343
Number of pages6
JournalClinical and Experimental Immunology
Volume105
Issue number2
Publication statusPublished - 1996

Keywords

  • Cyclosporin A
  • Deoxyspergualin
  • Diabetes-prone BB rat
  • Immunotherapy
  • Insulin-dependent diabetes mellitus

ASJC Scopus subject areas

  • Immunology

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