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Drugs that block IDO activity have been tested in vitro and in murine models of different diseases . Several molecules have been developed and tested in vitro, but only two have been tested in vivo, with variable and not always reproducible results. N-Methyl-D-tryptophan (D-1mT) has shown good tolerability and efficacy in murine models of SLE, hepatitis and nephritis, and D-1mT treatment of human anti-DNA auto-antibody (anti-DNA) positive SLE patients resulted in significantly reduced serum levels of anti-DNA IgG, suggesting that D-1mT may be a potential therapeutic option in SLE patients. However, long-term treatment with D-1mT in the SLE murine model was associated with increased auto-antibody responses, including anti-nuclear antibodies, anti-cardiolipin antibodies, and anti-SS-A/Ro and anti-SS-B/La antibodies, an effect which was not observed in non-auto-immune animals. The administration of D-1mT to SIV-infected Rhesus macaques also induced auto-antibody production [8,9]. Unfortunately, a recent multicenter phase 2 clinical trial of D-1mT in 240 SLE patients did not show significant differences in the primary outcome measures [10,11].
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