SYSTEMIC DELIVERY OF INTERLEUKIN-10 BY INTRAMUSCULAR INJECTION OF EXPRESSION PLASMID DNA PREVENTS AUTOIMMUNE DIABETES IN NONOBESE DIABETIC MICE

We previously demonstrated that intramuscular plasmid injection serves as a useful method of long-term systemic delivery of cytokines, In th e present study, we assess intramuscular DNA injection as a means of s ystemically delivering interleukin 10 (IL-10), a cytokine with immunos uppressive properties, and preventing the progression of autoimmune di abetes in the nonobese diabetic (NOD) mouse, an excellent model for hu man insulin-dependent diabetes mellitus (IDDM), We injected IL-10 expr ession plasmid (pCAGGS-IL10) or a control pCAGGS plasmid into the musc les of NOD mice twice at 3 and 5 weeks of age. IL-10 was detectable by ELISA in the sera of mice injected with pCAGGS-IL10 for more than 2 w eeks after the injection. Although the severity of insulitis at 13 wee ks of age was not improved by the intramuscular injection of pCAGGS-IL 10, the incidence of diabetes was markedly reduced in NOD mice injecte d with pCAGGS-IL10 as compared with those injected with pCAGGS or as c ompared with nontreated NOD mice. These results show that the progress ion of autoimmune diseases in mice can effectively be suppressed by in tramuscular DNA injection, and suggest that this method is potentially applicable to the treatment of human autoimmune diseases.