Suppression of collagen induced arthritis in mice utilizing plasmid DNA encoding interleukin 10.
OBJECTIVE
To investigate the therapeutic efficacy as well as the immunological effects of inoculation of an expression vector encoding interleukin 10 (IL-10) in murine type II collagen induced arthritis (CIA).


METHODS
CIA was induced in DBA/1 Lac/J mice by immunization with bovine type II collagen (CII) in Freund's complete adjuvant (FCA), followed by immunization of CII in Freund's incomplete adjuvant (FIA) 3 weeks later (CIA mice). The plasmid cytomegalovirus (pCMV) vector encoding IL-10 (pCMV-IL-10) was inoculated intradermally into DBA/1 Lac/J mice (pCMV-IL-10 CIA mice) one week prior to first immunization with CII. CIA mice inoculated with the backbone pCMV vector instead of pCMV-IL-10(pCMV CIA mice), mice inoculated with the pCMV vector alone, without subsequent immunization with CII (pCMV-C mice), and mice not subjected to any treatment (C mice) were examined as controls. At the 3rd and 5th week after 2nd immunization with CII, booster injections of CII in FIA were administered. Foot pad thicknesses were measured weekly and the histopathological changes in the ankle joints and the titers of IgG1 (Th2 type) and IgG2a (Th1 type) isotype antibodies to CII were examined at the 10th week.


RESULTS
pCMV-IL-10 CIA mice showed lesser foot pad thicknesses (p < 0.01 except at Weeks 1-3), less severe histopathological changes (p < 0.01 or 0.05) and lower IgG2a/IgG1 ratios of antibodies to CII (p <0.01) than CIA mice.


CONCLUSIONS
Inoculation of pCMV-IL-10 suppressed CIA through suppression of the Th 1 type immune response in CIA, and offers promise as a potential therapeutic strategy for rheumatoid arthritis.
Department of Internal Medicine II, Fukushima Medical University School of Medicine, Japan. metm@msg.biglobe.ne.jp
M
M
Miyata
T
T
Sasajima
H
H
Sato
A
A
Saito
A
A
Saito
A
A
Iriswa
Y
Y
Sato
R
R
Kasukawa
D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D002417:Cattle; D003094:Collagen / Q000009:adverse effects / Q000276:immunology; D005528:Foot / Q000473:pathology / Q000503:physiopathology; D015316:Genetic Therapy; D005822:Genetic Vectors; D016753:Interleukin-10 / Q000235:genetics*; D051379:Mice; D008811:Mice, Inbred DBA; D018146:Muromegalovirus / Q000235:genetics; D010957:Plasmids / Q000494:pharmacology*
D016753:Interleukin-10; D003094:Collagen