EXPERIMENTAL-THERAPY OF SYSTEMIC LUPUS-ERYTHEMATOSUS - THE TREATMENT OF NZB W MICE WITH MOUSE SOLUBLE INTERFERON-GAMMA RECEPTOR INHIBITS THE ONSET OF GLOMERULONEPHRITIS/

Female NZB/W F1 mice develop an autoimmune disease similar to human sy stemic lupus erythematosus (SLE), and ultimately die of glomerulonephr itis. Starting at the age of 16 weeks NZB/W Fl mice were treated for a period of 19 weeks with soluble interferon-gamma receptor (sIFN-gamma R), anti-IFN-gamma monoclonal antibody (mAb) or IFN-gamma. All mice t reated with sIFN-gamma R or anti-IFN-gamma mAb were alive 4 weeks afte r the treatment was discontinued, whereas 50% of mice died in the plac ebo groups and 78% of the mice died in the IFN-gamma-treated group. Hi stologically, there was severe membrano-proliferative glomerulonephrit is in IFN-gamma- and placebo-treated mice, and minimal or no mesangiop roliferative disease in mice receiving sIFN-gamma R or anti-IFN-gamma mAb. The renal mononuclear infiltrate (T lymphocytes and monocytes), e xpression of major histocompatibility complex class II antigen and glo merular immunoglobulin and complement deposition were reduced in those mice. These data suggest that an IFN-gamma inhibitor, such as the sol uble IFN-gamma R, can be used for SLE therapy in the early stages of t he disease.