IL-1 beta-deficient mice are resistant to induction of experimental SLE

Elena Voronov, Molly Dayan, Heidy Zinger, Lubov Gayvoronsky, Jian-Ping Lin, Yoichiro Iwakura, Ron N Apte, Edna Mozes

Research output: Contribution to journalArticlepeer-review

Abstract

IL-1 is one of the most pleiotropic pro-inflammatory and immunostimulatory cytokines. Overproduction of IL-1 has been shown to be involved in the pathogenicity of various autoimmune inflammatory diseases, including systemic lupus erythematosus (SLE). However, the different contributions that the IL-1 agonistic molecules make in their in vivo native milieu, IL-1beta which is mainly secreted against IL-1alpha which is mainly cell-associated, have not been established. Experimental SLE can be induced in mice by injection with monoclonal anti-DNA antibodies bearing a major idiotype designated, 16/6Id. In the present study, experimental SLE was induced in mice deficient in specific IL-1 molecules, i.e. IL-1alpha(-/-), IL-1beta(-/-), IL-1alpha/beta(-/-) (double KO) and in control BALB/c mice. Mice deficient in IL-1beta , i.e. IL-1beta(-/-) and IL-1alpha/beta(-/-) mice, developed lower levels of anti-dsDNA antibodies after immunization with 16/6Id, as compared to IL-1alpha(-/-) or control BALB/c mice. Disease manifestations were milder in mice deficient in IL-1beta expression. The representative cytokine cascade that is characteristic of overt experimental SLE was also shown to be reduced in groups of mice that lacked IL-1beta as compared to mice deficient in IL-1alpha, which is mainly cell-associated. Altogether, our results point to the importance of secretable IL-1beta, rather than cell-associated IL-1alpha, in the immunostimulatory and inflammatory phenomena that mediate the pathogenesis of experimental SLE.

Original languageEnglish
Pages (from-to)109-16
Number of pages8
JournalEuropean Cytokine Network
Volume17
Issue number2
StatePublished - Jun 2006

Keywords

  • Animals
  • Antibodies/blood
  • Disease Models, Animal
  • Female
  • Genetic Predisposition to Disease
  • Immunity, Innate/genetics
  • Interleukin-1/deficiency
  • Lupus Erythematosus, Systemic/blood
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout

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