Syngeneic fibroblasts transfected with a plasmid encoding interleukin-4 as non-viral vectors for anti-inflammatory gene therapy in collagen-induced arthritis.
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.
UPRES EA-3408, Léonard de Vinci Medical School and Department of Rheumatology (Avicenne Hospital, Bobigny, AP-HP), University of Paris 13, Paris, France. bessis@smbh.univ-paris13.fr
Natacha
N
Bessis
Virginie
V
Cottard
Nathalie
N
Saidenberg-Kermanach
Delphine
D
Lemeiter
Catherine
C
Fournier
Marie-Christophe
MC
Boissier
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000628:therapy*; D016466:CHO Cells; D002455:Cell Division; D002461:Cell Line, Transformed; D006224:Cricetinae; D005347:Fibroblasts / Q000378:metabolism; D015316:Genetic Therapy; D005822:Genetic Vectors; D015847:Interleukin-4 / Q000235:genetics*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010957:Plasmids; D013601:T-Lymphocytes / Q000166:cytology
D015847:Interleukin-4