Treatment of murine lupus with cDNA encoding IFN-gamma R/Fc

IFN-gamma, a pleiotropic cytokine, is a key effector molecule in the pathog enesis of several autoimmune diseases, including lupus. Importantly, deleti on of IFN-gamma or IFN-gamma R in several lupus-predisposed mouse strains r esulted in significant disease reduction, suggesting the potential for ther apeutic intervention. We evaluated whether intramuscular injections of plas mids with cDNA encoding IFN-gamma R/Fc can retard lupus development and pro gression in MRL-Fas(lpr) mice. Therapy significantly reduced serum levels o f IFN-gamma, as well as disease manifestations (autoantibodies, lymphoid hy perplasia, glomerulonephritis, mortality), when treatment was initiated at the predisease stage, particularly when IFN-gamma R/Fc expression was enhan ced by electroporation at the injection site. Remarkably, disease was arres ted and even ameliorated when this treatment was initiated at an advanced s tage. This therapy represents a rare example of disease reversal and makes application of this nonviral gene therapy in humans with lupus (and perhaps other autoimmune/inflammatory conditions) highly promising.