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IL-1Β-deficient mice are resistant to induction of experimental SLE Volume 17, numéro 2, June 2006

Auteurs
Department of Microbiology and Immunology, Faculty of Health Sciences and The Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel, Department of Immunology, The Weizmann Institute of Science, Rechovot 76100, Israel, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan

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-1β which is mainly secreted against IL-1α 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-1α -/-, IL-1β -/-, IL-1α/β -/- (double KO) and in control BALB/c mice. Mice deficient in IL-1β, i.e. IL-1β -/- and IL-1α/β -/- mice, developed lower levels of anti-dsDNA antibodies after immunization with 16/6Id, as compared to IL-1α -/- or control BALB/c mice. Disease manifestations were milder in mice deficient in IL-1β 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-1β as compared to mice deficient in IL-1α, which is mainly cell-associated. Altogether, our results point to the importance of secretable IL-1β, rather than cell-associated IL-1α, in the immunostimulatory and inflammatory phenomena that mediate the pathogenesis of experimental SLE.