The lupus-like autoimmune syndrome of MRL/Mp-Tnfrsf6lpr (lpr) 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-gamma plays a pivotal role in the abnormal cell activation and the fatal development of the lpr disease. IL-18, an inducer of IFN-gamma in T lymphocytes and natural killer cells, may contribute to the disease because cells from lpr 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 lpr 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-gamma 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 lpr mice and that a reduction in IL-18 activity could be a therapeutic strategy in autoimmune diseases.
|Titolo:||IL-18 cDNA vaccination protects mice from spontaneous lupus-like autoimmune disease|
|Parole Chiave:||Animals; Interferon-gamma; Lupus Nephritis; Humans; Mice; Mice, Inbred BALB C; Vaccines, DNA; Lymphocyte Activation; Autoantibodies; Lupus Erythematosus, Systemic; Mice, Inbred C57BL; Mice, Inbred MRL lpr; Interleukin-18; T-Lymphocytes|
|Settore Scientifico Disciplinare:||Settore MED/16 - Reumatologia|
|Data di pubblicazione:||25-nov-2003|
|Digital Object Identifier (DOI):||10.1073/pnas.2336094100|
|Appare nelle tipologie:||01 - Articolo su periodico|