Decreased response to IL-12 and IL-18 of peripheral blood cells in rheumatoid arthritis |
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Authors: | Masanori?Kawashima Email author" target="_blank">Pierre?MiossecEmail author |
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Affiliation: | (1) Department of Immunology and Rheumatology and INSERM U-403, Pavillon F, Hospital Edouard Herriot, 69437 Lyon Cedex 03, France; |
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Abstract: | Inflamed synovium of rheumatoid arthritis (RA) has been associated with a T helper (Th)1 cytokine profile but the blood situation
remains to be clarified. We studied the differential IFN-γ producing activity of peripheral blood mononuclear cells (PBMCs)
from RA patients (RA-PBMCs) and from healthy controls (H-PBMCs) in response to IL-12 and IL-18. RA-PBMCs had a decreased IFN-γ
production in response to IL-12 and IL-18 when compared with H-PBMCs. RA-PBMCs activated with phytohemagglutinin and phorbol
12-myristate 13-acetate showed an increased sensitivity to IL-12 and IL-18, but still the RA-PBMC response was lower. IL-18
increased IL-12-stimulated IFN-γ production from RA synovium cells obtained after collagenase digestion more effectively than
that of RA- or H-PBMCs. A specific inhibitor of IL-18 bioactivity, IL-18-binding protein (IL-18BP), down-regulated IL-12-induced
IFN-γ production by RA- or H-PBMCs and had a remarkable effect on RA synovium cells. In conclusion, RA disease combines a
polarized immune response with an active Th1 in inflamed joints and a reduced Th1 pattern in peripheral circulation. |
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