TY - EJOU
AU - Voronov, Elena
AU - Dayan, Molly
AU - Zinger, Heidy
AU - Gayvoronsky, Lubov
AU - Lin, Jian-Ping
AU - Iwakura, Yoichiro
AU - Apte, Ron N.
AU - Mozes, Edna
TI - IL-1β-deficient mice are resistant to induction of experimental SLE
T2 - European Cytokine Network
PY - 2006
VL - 17
IS - 2
SN - 1952-4005
AB - 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.
KW - experimental SLE
KW - IL-1α
KW - IL-1β
DO -