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

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-1α 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/ß^{-/ -} (double KO) and in control BALB/c mice. Mice deficient in IL-1β, i.e. IL-1β^-/- and IL-1α/ß^-/- 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.