Murine IL-10 gene transfer inhibits established collagen-induced arthritis and reduces adenovirus-mediated inflammatory responses in mouse liver.
The effects of homologous IL-10 administration during an established autoimmune disease are controversial, given its reported immunostimulatory and immunosuppressive properties. Studies of collagen-induced arthritis have shown 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 elucidate the effects of prolonged homologous IL-10 administration via adenovirus-mediated gene delivery on the progression of established arthritis. Collagen type II (CII)-immunized mice received i.v. injections of 10(7) or 10(8) PFU of an E1-deleted adenoviral vector containing the murine IL-10 gene (AdIL-10), after arthritis onset. Mice were monitored for 3 wk for disease progression, and gene transduction was assessed by quantification of serum mIL-10. CII-specific cell-mediated and humoral immune responses were analyzed by lymph node cell proliferation, cytokine production, and anti-CII Ab responses. Furthermore, because adenoviral vectors have been reported to induce organ dysfunction due to cell-mediated immune responses to the viral Ags, we have also evaluated delayed-type hypersensitivity responses and reactive hepatitis to the systemically delivered adenovirus and whether the IL-10 produced could influence those responses. Sustained suppression of autoimmune arthritis and elevated serum levels of IL-10 were achieved in our study. AdIL-10 treatment reduced cell-mediated immune reactivity, but did not affect humoral responses. Furthermore, IL-10 was able to reduce, but not totally abrogate, adenovirus-induced hepatic inflammation. These findings provide further insights into the diverse interplay of immune processes involved in autoimmune inflammation and the mechanism of cytokine immunotherapy.
Quattrocchi
E
E
Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, Hammersmith, London, United Kingdom.
Dallman
M J
MJ
Dhillon
A P
AP
Quaglia
A
A
Bagnato
G
G
Feldmann
M
M
D000260:Adenoviruses, Human / Q000235:genetics* / Q000276:immunology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D003094:Collagen / Q000037:antagonists & inhibitors; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D006614:Hindlimb; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000473:pathology / Q000821:virology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D016753:Interleukin-10 / Q000008:administration & dosage / Q000235:genetics*; D008099:Liver / Q000276:immunology / Q000473:pathology* / Q000821:virology; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000276:immunology; D014161:Transduction, Genetic
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D003094:Collagen