Interleukin-13 prevents autoimmune diabetes in NOD mice

Interleukin (IL)-13 is a cytokine primarily produced by the T-helper (Th)-2 subset of lymphocytes that possesses powerful anti-inflammatory properties . Here, we have evaluated the impact of IL-13 treatment on development of t ype 1 diabetes in diabetes-prone nonobese diabetic (NOD) mice. Prolonged tr eatment with recombinant human IL-13 (hIL-13) markedly diminished the incid ence of spontaneous type 1 diabetes in the mice. Female NOD mice treated fr om age 5-16 weeks with hIL-13 also showed significantly milder insulitis th an control mice. The preventive action of hIL-13 was associated with a slig ht but significant change from a type I to a type 2 cytokine response. Acco rdingly, splenic lymphoid cells (SLC) from hIL-13-treated mice secreted les s interferon (IFN)-gamma upon ex vivo stimulation with Concanavalin A than controls, and anti-CD3 monoclonal antibody-induced activation of T-cells in vivo resulted in lower blood levels of IFN-gamma and tumor necrosis factor -alpha and augmented blood levels of IL-4 in NOD mice pretreated with hIL-1 3. hIL-13 treatment also increased the blood levels of IgE and inhibited th e transfer of type 1 diabetes by spleen cells from a diabetic donor to irra diated recipients. Taken together, these data add hIL-13 to the list of cyt okines capable of downregulating immunoinflammatory diabetogenic pathways i n NOD mice, and further support the concept that IL-4-related anti-inflamma tory cytokines might have a role in the prevention of type 1 diabetes.