title: A comparative study on intra-articular versus systemic gene electrotransfer in experimental arthritis.
abstract: BACKGROUND
  Electric pulse mediated gene transfer has been applied successfully in vivo for increasing naked DNA administration in various tissues. To achieve non-viral gene transfer into arthritic joint tissue, we investigated the use of electrotransfer (ET). Because anti-inflammatory cytokine strategies have proven efficient in experimental models of arthritis, we compared the therapeutic efficiency of local versus systemic delivery of the interleukin-10 (IL-10) using in vivo ET.
  
  
  METHODS
  A plasmid vector expressing IL-10 was transferred into DBA/1 mouse knee joints by ET with 12 pulses of variable duration and voltage. The kinetics of transgene expression were analyzed by specific enzyme-linked immunosorbent assay (ELISA) in sera and knees. Optimal conditions were then used to deliver increasing amounts of IL-10 plasmid intra-articularly (i.a.) in the collagen-induced arthritis (CIA) mouse model. The therapeutic efficiency was compared with the potency of intra-muscular (i.m.) ET.
  
  
  RESULTS
  Following i.a. ET, local IL-10 secretion peaked on day 7 and dropped 2 weeks after. A second ET produced the same kinetics without enhancing gene transfer efficiency, while transgene was still detected in injected muscles 4 weeks after ET. Only the i.m. ET of 25 microg of IL-10 significantly inhibited all the clinical and biological features of arthritis. The i.a. ET only showed mild improvement of arthritis when 100 microg of IL-10 plasmid were electrotransfered weekly from day 18 following arthritis induction.
  
  
  CONCLUSIONS
  The present results suggest that gene transfer into arthritic joints by ET is an effective means to deliver anti-inflammatory cytokines. However, short duration of transgene expression impedes a significant effect for the treatment of arthritis, making i.m. ET more potent than i.a. ET for clinical benefit in CIA.
authors.affiliation: Inserm, U 475, F-34000 Montpellier, France.
authors.forename: M
authors.initials: M
authors.lastname: Khoury
authors.forename: P
authors.initials: P
authors.lastname: Bigey
authors.forename: P
authors.initials: P
authors.lastname: Louis-Plence
authors.forename: D
authors.initials: D
authors.lastname: Noel
authors.forename: H
authors.initials: H
authors.lastname: Rhinn
authors.forename: D
authors.initials: D
authors.lastname: Scherman
authors.forename: C
authors.initials: C
authors.lastname: Jorgensen
authors.forename: F
authors.initials: F
authors.lastname: Apparailly
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D002358:Cartilage, Articular / Q000378:metabolism*; D002417:Cattle; D049109:Cell Proliferation; D003094:Collagen / Q000276:immunology / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D018274:Electroporation; D005240:Feasibility Studies; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D007700:Kinetics; D007719:Knee Joint / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010957:Plasmids; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors; D019076:Transgenes
chemical_list: D016207:Cytokines; D003094:Collagen