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Collagen-induced arthritis can be transferred into severe combined immunodeficiency (SCID) mice by spleen cells from diseased DBA/1 mice. The development of arthritis in SCID animals can be prevented by infection ex vivo of DBA/1 spleen cells with retroviruses expressing the monomeric soluble human p75 tumor necrosis factor (TNF) receptor (TNF-R). In addition, a vector engineered to express a polycystronic mRNA with TNF-R and the herpes simplex virus thymidine kinase (HSVtk) gene, while producing low levels of TNF-R, had a limited effect which could be blocked by treating the animals with ganciclovir. A retroviral vector expressing the HSVtk gene alone had no effect on this arthritis transfer model with or without ganciclovir. Serum levels of TNF-R did not correlate with clinical signs, however, lower anti-collagen antibody levels corresponded with lack of clinical symptoms. These results indicate that local production of cytokine inhibitor is essential for therapeutic purposes while systemic levels may not be required.

Type

Journal article

Journal

Gene therapy

Publication Date

12/1995

Volume

2

Pages

731 - 735

Addresses

Sunley Division, Kennedy Institute of Rheumatology, London, UK.

Keywords

Spleen, Cells, Cultured, Cell Line, Animals, Mice, Inbred DBA, Humans, Mice, Mice, SCID, Simplexvirus, Retroviridae, Arthritis, Experimental, Ganciclovir, Collagen, Thymidine Kinase, Receptors, Tumor Necrosis Factor, Recombinant Proteins, Enzyme-Linked Immunosorbent Assay, Lymphocyte Transfusion, Gene Therapy, Transfection, Male