Plasmid encoding interleukin-4 in the amelioration of murine collagen-induced arthritis.
OBJECTIVE
To evaluate the therapeutic effect of the administration of plasmid encoding interleukin-4 (IL-4) via gene-gun delivery and via intradermal injection on collagen-induced arthritis (CIA).


METHODS
IL-4 plasmid was administered by gene-gun delivery and intradermal injection to DBA/1 mice immunized with type II collagen (CII). The therapeutic effect on the development of CIA was evaluated clinically with a visual scoring method for arthritis and serologically by enzyme-linked immunosorbent assays and polymerase chain reaction.


RESULTS
Treatment with IL-4-expressing plasmid significantly reduced the incidence and severity of CIA, including a reduction in the anti-CII antibody level. In particular, gene-gun delivery had a higher immunosuppressive effect on CIA compared with intradermal injection. As shown by in vitro stimulation assay, the spleen cells from mice immunized with CII and treated with IL-4 plasmid via gene gun exhibited higher Th2 cytokine responses compared with cells treated with control plasmid after in vitro stimulation with CII.


CONCLUSIONS
The results of this study suggest that treatment with IL-4 plasmid may constitute a new clinical use of cytokine gene therapy for rheumatoid arthritis.
Kageyama
Yasunori
Y
Departmentof Orthopaedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan. Tsukatonpipi@nifty.com
Koide
Yukio
Y
Uchijima
Masashi
M
Nagata
Toshi
T
Yoshida
Atsushi
A
Taiki
Aoshi
A
Miura
Tomohiko
T
Nagafusa
Tetsuyuki
T
Nagano
Akira
A
D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology* / Q000517:prevention & control / Q000628:therapy*; D019470:Biolistics; D024043:Collagen Type II / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D015316:Genetic Therapy; D007114:Immunization; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D066298:In Vitro Techniques; D007271:Injections, Intradermal; D015847:Interleukin-4 / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D010957:Plasmids / Q000235:genetics*; D012720:Severity of Illness Index; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D024043:Collagen Type II; D016207:Cytokines; D007166:Immunosuppressive Agents; D015847:Interleukin-4