Murine IL-10 gene transfer inhibits established collagen-induced arthritisand reduces adenovirus-mediated inflammatory responses in mouse liver

The effects of homologous IL-10 administration during an established autoim mune disease are controversial, given its reported immunostimulatory and im munosuppressive properties. Studies of collagen-induced arthritis have show n efficacy with repeated administrations of IL-10; however, when the EBV IL -10 homologue was administered via adenovirus gene transfer technology the results were equivocal. Therefore, the present study was undertaken to eluc idate the effects of prolonged homologous IL-10 administration via adenovir us-mediated gene delivery on the progression of established arthritis. Coll agen type II (CII)-immunized mice received Lv. injections of 10(7) or 10(8) PFU of an E1-deleted adenoviral vector containing the murine IL-10 gene (A dIL-10), after arthritis onset. Mice were monitored for 3 wk for disease pr ogression, and gene transduction was assessed by quantification of serum mI L-10. CII-specific cell-mediated and humoral immune responses were analyzed by lymph node cell proliferation, cytokine production, and anti-CII Ab res ponses. Furthermore, because adenoviral vectors have been reported to induc e organ dysfunction due to cell-mediated immune responses to the viral Ags, we have also evaluated delayed-type hypersensitivity responses and reactiv e hepatitis to the systemically delivered adenovirus and whether the IL-10 produced could influence those responses. Sustained suppression of autoimmu ne arthritis and elevated serum levels of IL-10 were achieved in our study. AdIL-10 treatment reduced cell-mediated immune reactivity, but did not aff ect humoral responses. Furthermore, IL-10 was able to reduce, but not total ly abrogate, adenovirus-induced hepatic inflammation. These findings provid e further insights into the diverse interplay of immune processes involved in autoimmune inflammation and the mechanism of cytokine immunotherapy.