DIABETES-MELLITUS INDUCED BY LOW-DOSE INTERLEUKIN-2

Interleukin-2 (IL-2) is a potent immunomodulator that has been associa ted with the clinical development of autoimmune disorders. However, di abetes mellitus has not been reported in patients treated with single- agent IL-2. We conducted a clinical trial of a protracted daily schedu le of subcutaneously administered low-dose IL-2. A patient with advanc ed colorectal cancer, treated with 1.5 x 10(6) international units of IL-2 daily, developed insulin-requiring diabetes during therapy. Hyper glycemia improved during treatment interruption and recurred with rein stitution of IL-2. The diabetes in this patient developed in the conte xt of T cell and natural killer cell expansion, and the presence of is let cell autoantibodies was documented. We postulate that, in this pat ient, IL-2 reversed the anergy of autoreactive T cells that had escape d clonal deletion. It is possible that prolonged daily exposure to imm unomodulatory doses of IL-2 will result in the development of autoimmu ne phenomena not observed with other schedules of administration.