Previous studies have shown that anti-γ-interferon (IFN-γ) antibody reduces the frequency of autoimmune IDDM in the DP-BB rat. We tested the effects of systemically administered recombinant rat IFN-γ in both DP-BB and DR-BB rats. Unexpectedly, IFN-γ 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-γ administered from age 30 to 105 days. Ex vivo production of tumor necrosis factor-a from splenic lymphoid cells (SLCs) and peritoneal macrophages of the rats treated with IFN-γ was comparable with that of controls; however, SLCs from the IFN-γ-treated animals secreted lower amounts of IFN-γ after stimulation with concanavalin A. IFN-γ 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-γ 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.

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