A NONCYTOLYTIC IL-10 FC FUSION PROTEIN PREVENTS DIABETES, BLOCKS AUTOIMMUNITY, AND PROMOTES SUPPRESSOR PHENOMENA IN NOD MICE/

We have been successful in our efforts to develop a long lived noncyto lytic murine IL-10/Fc fusion protein, In the nonobese diabetic mouse ( NOD) model, administration of IL-10/Fc from 5 to 25 wk of age complete ly prevented the occurrence of diabetes, Moreover, these mice remained disease-free long after cessation of IL-10/Fc therapy, Immunohistoche mistry studies show that IL-10/Fc treatment inhibits expression of TNF -alpha, proinflammatory cytokine, as well as Th1-type cytokines, IL-2 and IFN-gamma, but promotes expression of IL-4 and IL-10, Th2-type cyt okines, by islet-infiltrating leukocytes. In an adoptive transfer mode l of diabetes in NOD mice, we found that: 1) IL-10/Fc treated hosts be ar leukocytes that block expression of diabetes and 2) these leukocyte s persisted even 8 wk after cessation of IL-10/Fc treatment. The poten t antidiabetogenic effects provided by IL-10/Fc in the NOD model, toge ther with its apparent lack of systemic toxicity, are notable.