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Modulation of disease activity in murine systemic lupus erythematosus by cytokine gene delivery

Department of Medicine, University of California, San Diego, 9500 Gilman Drive, Mail code 0663, La Jolla, CA 92093-0663, The Sam and Rose Stein Institute for Research on Aging, La Jolla, CA

J. Dudler

Department of Medicine, University of California, San Diego, 9500 Gilman Drive, Mail code 0663, La Jolla, CA 92093-0663, The Sam and Rose Stein Institute for Research on Aging, La Jolla, CA

M. Lotz

Department of Medicine, University of California, San Diego, 9500 Gilman Drive, Mail code 0663, La Jolla, CA 92093-0663, The Sam and Rose Stein Institute for Research on Aging, La Jolla, CA

S.M. Baird

Department of Pathology, University of California, San Diego

C.C. Berry

Department of Family and Preventive Medicine, University of California, San Diego

R.A. Eisenberg

Department of Medicine, University of North Carolina, Chapel Hill, NC, USA

D.A. Carson

The Sam and Rose Stein Institute for Research on Aging, La Jolla, CA

Somatic gene therapy is a novel approach with the potential to achieve prolonged increases in circulating levels of peptide hormones and cytokines. The present study evaluates the effects of monthly, intramuscular injections of cDNA expression vectors encoding for transforming growth factor ß (TGFß) or interleukin 2 (IL-2) on disease activity in the MRL/lpr/lpr murine model of systemic lupus erythematosus (SLE). Monthly injections of plasmids cDNA between 6 and 26 weeks significantly elevated the serum levels of TGFß (P < 0.005) and IL-2 (P < 0.05) compared with a control plasmid without insert. TGFß encoding plasmid had beneficial effects in murine SLE with a prolonged survival of 70% at 26 weeks compared with 40% in the control group, decreased anti-chromatin and rheumatoid factor antibodies and a 50% decrease in total IgG production. Renal function was improved with reduced BUN levels and kidney inflammation as estimated by an histologic score. Those beneficial effects occurred in the apparent absence of local or systemic side-effects. In contrast, IL-2 cDNA injections appeared harmful with a decreased survival to 20% at 26 weeks, enhanced total IgG synthesis and autoantibodies production with a 4.5-fold increase in anti-chromatin antibodies. These results indicate that somatic gene therapy may provide a simple, inexpensive and effective mechanism for the long-term control of autoimmune diseases.

Key Words: Gene therapy • TGFß • IL-2 • animal models

Lupus, Vol. 4, No. 4, 286-292 (1995)
DOI: 10.1177/096120339500400409


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