INTERLEUKIN-4 - POTENTIAL IMMUNOREGULATORY AGENT IN THERAPY OF INSULIN-DEPENDENT DIABETES-MELLITUS

The nonobese diabetic (NOD) mouse spontaneously develops a diabetic sy ndrome that closely resembles human insulin-dependent diabetes mellitu s (IDDM). T cell-mediated destruction of pancreatic cells may result f rom an unresponsiveness in regulatory T helper 2 (T(H)2) cells, favour ing a T helper 1 (T(H)1) cell-mediated environment, in the pancreas. I n the NOD mouse, this T cell unresponsiveness can be reversed complete ly in vitro by exogenous interleukin-4 (IL-4), and in vivo administrat ion of recombinant IL-4 (rIL-4) completely prevents insulitis and the onset of diabetes. These effects may in part be a consequence of an IL -4-directed shift from a T(H)1 (effector) dominant to a T(H)2 (protect ive) dominant immune response. The administration of IL-4 during the c ourse of an inflammatory autoimmune disease could prime developing aut oreactive T cells for IL-4 production and may prevent the tissue-damag ing effects of autoreactive T(H)1 cells. In this regard, IL-4 emerges as an excellent potential immunotherapeutic agent in IDDM and other hu man organ-specific autoimmune diseases.