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

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Title
Inhibition of interleukin-12 production by auranofin, an anti-rheumatic gold compound, deviates CD4+ T cells from the Th1 to the Th2 pathway
Author(s)
T S Kim; B Y Kang; M H Lee; Yong Kyung Choe; S Y Hwang
Bibliographic Citation
British Journal of Pharmacology, vol. 134, pp. 571-578
Publication Year
2001
Abstract
1. 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 Thl 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.
Keyword
AuranofinInterleukin-12MacrophageRheumatoid arthritisT helper cell
ISSN
0007-1188
Publisher
Wiley
DOI
http://dx.doi.org/10.1038/sj.bjp.0704298
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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