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 type 1 diabetes in diabetes-prone nonobese diabetic (NOD) mice. Prolonged treatment with recombinant human IL-13 (hIL-13) markedly diminished the incidence of spontaneous type 1 diabetes in the mice. Female NOD mice treated from age 5-16 weeks with hIL-13 also showed significantly milder insulitis than control mice. The preventive action of hIL-13 was associated with a slight but significant change from a type 1 to a type 2 cytokine response. Accordingly, splenic lymphoid cells (SLC) from hIL-13-treated mice secreted less 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-13. hIL-13 treatment also increased the blood levels of IgE and inhibited the transfer of type 1 diabetes by spleen cells from a diabetic donor to irradiated recipients. Taken together, these data add hIL-13 to the list of cytokines capable of downregulating immunoinflammatory diabetogenic pathways in NOD mice, and further support the concept that IL-4-related anti-inflammatory cytokines might have a role in the prevention of type 1 diabetes.
Zaccone
P
P
Institute of Microbiology, University of Catania, Italy.
Phillips
J
J
Conget
I
I
Gomis
R
R
Haskins
K
K
Minty
A
A
Bendtzen
K
K
Cooke
A
A
Nicoletti
F
F
D000818:Animals; D001327:Autoimmune Diseases / Q000517:prevention & control*; D017690:Cell Transplantation; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000517:prevention & control; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000097:blood; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors
D018793:Interleukin-13; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma