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.
|Titolo:||Paradoxical antidiabetogenic effect of gamma-interferon in DP-BB rats|
MERONI, PIERLUIGI (Penultimo)
|Parole Chiave:||Histocompatibility Antigens Class II ; Injections, Intraperitoneal ; Animals ; Tumor Necrosis Factor-alpha ; Interferon-gamma ; Recombinant Proteins ; Random Allocation ; Dose-Response Relationship, Drug ; Aging ; Spleen ; Tacrolimus ; Receptors, Interleukin-2 ; Immunosuppressive Agents ; Rats ; Phenotype ; Rats, Inbred BB ; Concanavalin A ; Hypoglycemic Agents ; Diabetes Mellitus, Type 1 ; Macrophages, Peritoneal ; Incidence ; Male ; Female ; Diabetes Mellitus, Experimental|
|Settore Scientifico Disciplinare:||Settore MED/16 - Reumatologia|
|Data di pubblicazione:||gen-1998|
|Appare nelle tipologie:||01 - Articolo su periodico|