Synergistic effect of deoxyspergualin (DSP) and cyclosporin A (CsA) in the prevention of spontaneous autoimmune diabetes in BB rats.
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 BB rats when administered alone under a prolonged prophylactic regimen (30-105 days old), may successfully prevent, but not cure, the disease when given contemporaneously 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.
Di Marco
R
R
Institute of Microbiology, University of Catania, Italy.
Zaccone
P
P
Magro
G
G
Grasso
S
S
Lunetta
M
M
Barcellini
W
W
Nicolosi
V M
VM
Meroni
P L
PL
Nicoletti
F
F
D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006146:Guanidines / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D011913:Rats, Inbred BB
D006146:Guanidines; D007166:Immunosuppressive Agents; D016572:Cyclosporine; C037258:gusperimus