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Decreased response to IL-12 and IL-18 of peripheral blood cells in rheumatoid arthritis.

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-gamma 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-gamma 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-gamma 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-gamma 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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Submitted on : Wednesday, November 15, 2006 - 8:51:50 PM
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Masanori Kawashima, Pierre Miossec. Decreased response to IL-12 and IL-18 of peripheral blood cells in rheumatoid arthritis.. Arthritis Research and Therapy, BioMed Central, 2004, 6 (1), pp.R39-R45. ⟨10.1186/ar1020⟩. ⟨inserm-00114077⟩

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