The effect of IL-12 on clinical and laboratory aspects of experimental SLE in young and aging mice.
IL-12 plays a crucial role in a variety of immune responses that are involved in immuno-senesence and autoimmune diseases. Experimental SLE can be induced in mice by the monoclonal anti-DNA autoantibody bearing the 16/6Id. Aging mice are less susceptible to disease induction. We evaluated the in vivo effects of IL-12 on several parameters related to aging and to experimental SLE. Young (2 months) and aging (10 months) mice that were or were not immunized with the 16/6Id were treated with IL-12. IL-12 treated unimmunized BALB/c and C3H.SW mice had significant elevated levels of anti-DNA antibodies. A high percentage of these mice had glomerular immune complex deposits (ICD). IL-12 treatment resulted in significant increase of IL-1 and IFN-gamma and a decrease of IL-10 production in unimmunized mice. The same IL-12 induced changes were observed in mice with experimental SLE but were less pronounced than in normal mice. In general, all the effects in SLE afflicted mice were more prominent in aging than in young mice. Treatment of mice with experimental SLE upregulated IL-1, IL-2, IFNgamma and downregulated IL-10. These changes were observed in the groups of young as well as old mice. In conclusion, administration of IL-12 to aging mice reversed their Th1/Th2 cytokine profile and thus rendered them vulnerable to the induction of experimental SLE.
Segal
Rephael
R
Department of Immunology, The Weizmann Institute of Science, 76100, Rehovot, Israel.
Dayan
Molly
M
Zinger
Heidy
H
Habut
Beno
B
Shearer
Gene M
GM
Mozes
Edna
E
D000375:Aging / Q000276:immunology*; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D000936:Antigen-Antibody Complex / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000276:immunology; D005260:Female; D018664:Interleukin-12 / Q000276:immunology*; D007678:Kidney Glomerulus / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D016207:Cytokines; D018664:Interleukin-12; D004247:DNA