Inhibition of interleukin-12 production by auranofin, an anti-rheumatic gold compound, deviates CD4^+ T cells from the Th1 to the Th2 pathway

다국어 초록 (Multilingual Abstract)

I Interleukin-12 (IL-12) may play a central role in the development and progression of rheumatoid arthritis by driving the immune response towards T helper 1 (Th1) type responses characterized by high IFN-γ and low IL-4 production. In this study we investigated the effect of auranofin (AF). an anti-rheumatic gold compound, on IL-12 production in mouse macrophages and dendritic cells, and studied whether AF-mediated inhibition of IL-12 production could regulate a cytokine profile of antigen (Ag)-primed CD4^+ Th cells.
2 Treatment with AF significantly inhibited IL-12 production in lipopolysaccharide (LPS)-stimulated macrophages and also in CD40L-stimulated dendritic cells. AF-pretreated macrophages reduced their ability to induce IFN-γ and increased the ability to induce IL-4 in Ag-primed CD4^+ T cells. AF did not influence the cell surface expression of the class Ⅱ MHC molecule and the costimulatory molecules CD80 and CD86.
3 Addition of recombinant IL-12 to cultures of AF-pretreated macrophages and CD4^+ T cells restored IFN-γ production in Ag-primed CD4^+ T cells.
4 The in vivo administration of AF resulted in the inhibition of IL-12 production by macrophages stimulated in vitro with LPS or heat-killed Listeria monocytogenes (HKL), leading to the inhibition of Th1 cytokine profile (decreased IFN-γ and increased IL-4 production) in Ag-primed CD4^+ T cells.
5 These findings may explain some known effects of AF including anti-rheumatic effects and the inhibition of encephalitogenicity, and point to a possible therapeutic use of AF in the Th1-mediated immune diseases such as autoimmune diseases.