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Title: Expression of interleukin-1β, tumor necrosis factor α, interleukins-6, -10 and -4, and metalloproteases by freshly isolated mononuclear cells from early never-treated and non-acute treated rheumatoid arthritis patients
Author: Vazquez-del Mercado, M.
Delgado-Rizo, V.
Munoz-Valle, J.F.
Orozco-Alcala, J.
Volk, H.-D.
Armendariz-Borunda, J.
Issue Date: 1999
Abstract: Objective: To determine IL-1β, TNFα, IL-6, IL-4, IL-10, MMP-1, MMP-3 and MMP-13 expression by freshly isolated peripheral blood (PBMC) and synovial fluid mononuclear cells (SFMC) in early, never-treated (ENT-RA) and non-acute, treated rheumatoid arthritis (NAT-RA) patients. To elucidate whether excessive or inadequate interleukin (IL) and metalloprotease (MMP) expression is influenced by the disease duration. Methods: Fourteen RA patients, 7 with early RA (< 1 year of evolution) never treated with corticosteroids or disease-modifying antirheumatic drugs, and 7 patients with non-acute RA (> 2 years of evolution) treated with disease-modifying antirheumatic drugs, were studied by ELISA and quantitative and semiquantitative RT-PCR. A group of 14 healthy subjects matched for sex and age was included. Results: No statistically significant difference in the protein or transcript levels for the cytokines of interest was found between the ENT-RA and NAT-RA groups. The cytokine mRNA expression by freshly isolated PBMC and SFMC in both groups was as follows: IL-1β > TNFα > IL-10 > IL-6, with no mRNA IL-4 expression. In contrast, cytokine serum levels in ENT-RA and NAT-RA patients were detected in inverse order as follows: IL-6 > IL-10, while IL-1β, TNFα and IL-4 were undetectable. MMP-3 mRNA expression by the PBMC of NAT-RA patients was statistically different to that in ENT-RA patients. Similar levels of mRNA expression of MMP-1, MMP-3 and MMP-13 by the PBMC and SFMC in both RA groups were observed. Conclusions A close equilibrium between MMP and pro/anti-inflammatory cytokine production is observed in ENT-RA and NAT-RA patients. This balance is apparently not influenced by the length of the disease. Highly sensitive methods such as quantitative RT-PCR and ELISA, and even studying freshly isolated MC, showed sustained cytokine secretion at the local level (synovial fluid/SFMC) and scarce translation at the peripheral level (serum/PBMC). Expression of MMP mRNA needs to be further evaluated in order to know whether their peripheral expression reflects their local activity in RA patients.
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