CYTARTHRITIS: Induction of regulatory-protective cytokines in chronic arthritis

• Research unit: EU RFP
• Project number: 95.0349

Key words (English)

Chondrocytes; cytokines; IL-4; IL-10 ; IL-13

Alternative project number (English)

EU project number: BMH4CT961698

Research programs (English)

EU-programme: 4. Frame Research Programme - 4.2 Agriculture and agroindustry

Short description (English)

See abstract

Further information (English)

Full name of research-institution/enterprise:
Hôpitaux universitaires de Genève HUG
Département de Médecine
Division de Rhumatologie

Partners and International Organizations (English)

Prof P Miossec, Prof J Natvig, Prof G Duff, Dr J Alvaro-Gracia, Prof W van den Berg

Abstract (English)

Analysis of TH2 cytokine polymorphisms in rheumatoid arthritis (RA). Comparison with polymyalgia rheumatica (PMR)
Analysis of the allelic distributions of polymorphisms of the genes coding for IL-4, and search for evidence for an involvement of this gene in the erosive outcome of a Swiss group of RA patients (273 patients showed a very significant association of the rare allele of the IL-4 VNTR with a less severe articular course (decreased destruction as assessed by evolution of the Larsen score). This association was observed in shared epitope (SE) positive and negative patients. Polymorphisms on other cytokine genes, including IL-10, IL-13, IL-1 and IL-1Ra were not found to be associated with the severity of articular destruction. No difference were found between RA PMR and controls. These results indicate that IL-4 is involved, besides HLA-DRB1 genes, in the articular outcome in RA.
Interleukin-4 and interleukin-13 protect human primary synovial cells from nitric oxide induced apo enhanced the degree of synovial expansion, suggesting possible detrimental effects. In this work we show that pretreatment by IL-4 or IL-13, but not IL-10, can protect human primary synoviocytes from apoptosis induced by the NO donor sodium-nitro-prusside (up to 100% and 73% protection, respectively). Cell survival was dependent on interleukin concentration, and duration of pretreatment. Anti-apoptotic effect was abolished by 0.1µM staurosporine and dramatically inhibited by wortmannin and LY294002, implying the involvement of PKC and IRS pathways, respectively. These results suggest that IL-4 may enhance synovial expansion in vivo by its anti-apoptotic effect, and open new insights on the use of IL-4 in gene therapy.

References in databases (English)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 95.0349