title: IL-1 beta-deficient mice are resistant to induction of experimental SLE.
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.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Health Sciences and The Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
authors.forename: Elena
authors.initials: E
authors.lastname: Voronov
authors.forename: Molly
authors.initials: M
authors.lastname: Dayan
authors.forename: Heidy
authors.initials: H
authors.lastname: Zinger
authors.forename: Lubov
authors.initials: L
authors.lastname: Gayvoronsky
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Lin
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Ron N
authors.initials: RN
authors.lastname: Apte
authors.forename: Edna
authors.initials: E
authors.lastname: Mozes
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D007375:Interleukin-1 / Q000172:deficiency / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout
chemical_list: D000906:Antibodies; D007375:Interleukin-1