IL-18 cDNA vaccination protects mice from spontaneous lupus-like autoimmune disease

Paola Bossù, Detlef Neumann, Elda Del Giudice, Antonio Ciaramella, Isabelle Gloaguen, Giamila Fantuzzi, Charles A. Dinarello, Emma Di Carlo, Piero Musiani, Pier Luigi Meroni, Gianfranco Caselli, Paolo Ruggiero, Diana Boraschi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)14181-14186
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue numberSUPPL. 2
DOIs
Publication statusPublished - Nov 25 2003

ASJC Scopus subject areas

  • Genetics
  • General

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