The lupus-like autoimmune syndrome of MRL/Mp-Tnfrsf6Ipr (Ipr) mice is characterized by progressive lymphadenopathy and autoantibody production, leading to early death from renal failure. Activation of T helper lymphocytes is one of the events in the pathogenesis of the disease in these mice and likely in human systemic lupus erythematosus. Among T helper lymphocyte-dependent cytokines, IFN-γ plays a pivotal role in the abnormal cell activation and the fatal development of the Ipr disease. IL-18, an inducer of IFN-γ in T lymphocytes and natural killer cells, may contribute to the disease because cells from Ipr mice are hypersensitive to IL-18 and express high levels of IL-18. To assess the contribution of IL-18 to the pathogenesis in the animal model, in vivo inhibition of IL-18 was attempted. Young Ipr mice were vaccinated against autologous IL-18 by repeated administration of a cDNA coding for the murine IL-18 precursor. Vaccinated mice produced autoantibodies to murine IL-18 and exhibited a significant reduction in spontaneous lymphoproliferation and IFN-γ production as well as less glomerulonephritis and renal damage. Moreover, mortality was significantly delayed in anti-IL-18-vaccinated mice. These studies support the concept that IL-18 plays a major role in the pathogenesis of the autoimmune syndrome of Ipr mice and that a reduction in IL-18 activity could be a therapeutic strategy in autoimmune diseases.
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Issue number||SUPPL. 2|
|Publication status||Published - Nov 25 2003|
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