EFFECT OF LATE MODULATION OF NITRIC-OXIDE PRODUCTION ON MURINE LUPUS

MRL/MpJ-Fas(lpr) (MRL-lpr) and New Zealand Black/White (NZB/W) mice de velop spontaneous autoimmune disease characterized by autoantibody pro duction and glomerulonephritis that progresses in parallel with increa sing systemic nitric oxide (NO) production. A previously published stu dy from our laboratory indicated that oral administration of the nitri c oxide synthase inhibitor N-G-monomethyl-L-arginine (NMMA) before the onset of clinical disease significantly decreased renal and joint pat hology in MRL-lpr mice, To characterize the effect of late modulation of NO production in murine SLE, we administered oral NMMA and/or restr icted dietary arginine after disease onset in two murine models of SLE . When receiving combined NMMA and arginine restriction, MRL-Epr mice had reduced joint pathology scores and NZB/W mice had lower renal path ology scores than control mice. These results indicate that modulating NO production after the onset of disease diminishes disease severity in two models of SLE, although not as effectively as treating before d isease onset. (C) 1997 Academic Press.