Suppression of collagen induced arthritis in mice utilizing plasmid DNA encoding interleukin 10

Objective, To investigate the therapeutic efficacy as well as the immunolog ical 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 ty pe II collagen (CII) in Freund's complete adjuvant (FCA), followed by immun ization of CII in Freund's incomplete adjuvant (FIA) 3 weeks later (CIA mic e). The plasmid cytomegalovirus (pCMV) vector encoding IL-10 (pCMV-IL-10) w as inoculated intradermally into DBA/1 Lac/J mice (pCMV-IL-10 CVA mice) one week prior to first immunization with CII. CIA mice inoculated with the ba ckbone pCMV vector instead of pCMV-IL-10 (pCMV CIA mice), mice inoculated w ith the pCMV vector alone, without subsequent immunization with CII (pCMV-C mice), and mice not subjected to any treatment (C mice) were examined as c ontrols. At the 3rd and 5th week after 2nd immunization with CII, booster i njections of CII in PIA were administered. Foot pad thicknesses were measur ed weekly and the histopathological changes in the ankle joints and the tit ers 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 e xcept at Weeks 1-3), less severe histopathological changes (p < 0.01 or 0.0 5) and lower IgG2a/lgG1 ratios of antibodies to CII (p < 0.01) than CIA mic e. Conclusion, Inoculation of pCMV-IL-10 suppressed CIA through suppression of the Th1 type immune response in CIA, and offers promise as a potential the rapeutic strategy for rheumatoid arthritis.