학술논문
Paradoxical antidiabetogenic effect of gamma-interferon in DP-BB rats.
Document Type
Journal Article
Author
Nicoletti, Ferdinando; Zaccone, Paola; Di Marco, Roberto; Magro, Gaetano; Grasso, Sebastiano; Stivala, Franca; Calori, Gilliola; Mughini, Lanfranco; Meroni, Pier Luigi; Garotta, Gianni; Nicoletti, F; Zaccone, P; Di Marco, R; Magro, G; Grasso, S; Stivala, F; Calori, G; Mughini, L; Meroni, P L; Garotta, G
Source
Subject
*INTERFERONS
*TREATMENT of diabetes
*PHYSIOLOGY
*DIABETES prevention
*THERAPEUTIC use of interferons
*AGING
*ANIMALS
*CELL receptors
*DIABETES
*DOSE-effect relationship in pharmacology
*TACROLIMUS
*HISTOCOMPATIBILITY antigens
*HYPOGLYCEMIC agents
*IMMUNOSUPPRESSIVE agents
*INJECTIONS
*MACROPHAGES
*TYPE 1 diabetes
*PLANT proteins
*RATS
*RECOMBINANT proteins
*STATISTICAL sampling
*SPLEEN
*TUMOR necrosis factors
*PHENOTYPES
*DISEASE incidence
*PHARMACODYNAMICS
*PREVENTION
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Language
ISSN
0012-1797
Abstract
Previous studies have shown that anti-gamma-interferon (IFN-gamma) antibody reduces the frequency of autoimmune IDDM in the DP-BB rat. We tested the effects of systemically administered recombinant rat IFN-gamma in both DP-BB and DR-BB rats. Unexpectedly, IFN-gamma markedly reduced the incidence of IDDM as compared with control rats when administered six times per week at a dosage of 280,000 U between ages 30-35 to 105 days or ages 60-64 to 105 days. A lower dosage (28,000 U on alternate days) was also protective when administered to DP-BB rats between birth and age 60 days. However, long-lasting protection against IDDM development over the 1-year study period was achieved only by the highest dosage of IFN-gamma administered from age 30 to 105 days. Ex vivo production of tumor necrosis factor-alpha from splenic lymphoid cells (SLCs) and peritoneal macrophages of the rats treated with IFN-gamma was comparable with that of controls; however, SLCs from the IFN-gamma-treated animals secreted lower amounts of IFN-gamma after stimulation with concanavalin A. IFN-gamma treatment also markedly reduced the frequency of phenotypically activated SLC-expressing class II antigens and interleukin-2 receptor. Finally, in agreement with the observed antidiabetogenic effects, exogenously administered IFN-gamma induced neither insulitis nor IDDM development in DR-BB rats, a subline of DP-BB rats in which autoimmune diabetes rarely occurs spontaneously but can be induced by administration of polyinosinic-polycytidilic acid. [ABSTRACT FROM AUTHOR]