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

Abstract

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.

• Authors: E Quattrocchi, M J Dallman, A P Dhillon, A Quaglia, G Bagnato, M Feldmann
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 166 Issue 10 Pg. 5970-8 (May 15 2001) ISSN: 0022-1767 [Print] United States
• PMID: 11342612 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Epitopes, T-Lymphocyte
• Immunoglobulin G
• Immunosuppressive Agents
• Interleukin-10
• Collagen

Topics

• Adenoviruses, Human (genetics, immunology)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage)
• Arthritis, Experimental (genetics, immunology, prevention & control)
• Collagen (antagonists & inhibitors)
• Epitopes, T-Lymphocyte (immunology)
• Genetic Vectors (administration & dosage, immunology)
• Hindlimb
• Humans
• Hypersensitivity, Delayed (immunology, pathology, virology)
• Immunoglobulin G (biosynthesis, blood)
• Immunosuppressive Agents (administration & dosage)
• Injections, Intraperitoneal
• Injections, Intravenous
• Injections, Subcutaneous
• Interleukin-10 (administration & dosage, genetics)
• Liver (immunology, pathology, virology)
• Lymphocyte Activation (genetics)
• Male
• Mice
• Mice, Inbred DBA
• T-Lymphocytes (immunology)
• Transduction, Genetic