Syngeneic fibroblasts transfected with a plasmid encoding interleukin-4 as non-viral vectors for anti-inflammatory gene therapy in collagen-induced arthritis

✍ Scribed by Natacha Bessis; Virginie Cottard; Nathalie Saidenberg-Kermanach; Delphine Lemeiter; Catherine Fournier; Marie-Christophe Boissier

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 119 KB
• Volume: 4
• Category: Article
• ISSN: 1099-498X
• DOI: 10.1002/jgm.275

✦ Synopsis

Background:

No effective long-term treatment is available for rheumatoid arthritis. recent advances in gene therapy and cell therapy have demonstrated efficiency in collagen-induced arthritis (cia). interleukin-4 (il-4) is already known to be efficient in cia in systemic injection or administered by gene therapy. this study was designed to evaluate the effect of a non-viral gene therapy of cia, involving injection of syngeneic fibroblasts transfected with a plasmid encoding for il-4.

Methods:

Immortalised fibroblasts from dba/1 mice (dba/1/0 cells) were transfected with a plasmid expressing il-4 cdna (dba/1/il-4 cells). xenogeneic fibroblasts from chinese hamster ovary (cho) transfected with a plasmid expressing il-4 cdna (cho/il-4) were studied also. the cells were engrafted in mice developing cia by subcutaneous injection of 3 x 10(6) dba/1/0 or dba/1/il-4 or cho/il-4 cells.

Results:

Injection of dba/1/il-4 cells, on days 10 and 25 after immunisation, was associated with a significant and lasting improvement in the clinical and histological evidence of joint inflammation and destruction as compared with dba/1/0 and cho/il-4 cells. dba/1/il-4 cell treatment decreased also the production of igg2a antibody to cii and the proliferation of ciib-specific nodal t cells. later treatments (engraftments on days 23 and 35 after immunisation) exerted also an anti-inflammatory effect, as evaluated on clinical and histological signs of cia.

Conclusions:

Taken together, these findings indicate that systemic administration of syngeneic cells transfected with an anti-inflammatory cytokine gene, namely il-4, with a non-viral method is effective in cia and may attenuate the cytokine imbalance seen in this disease.