Methimazole prevents induction of experimental systemic lupus erythematosus in mice.
Experimental SLE can be induced in mice by immunization with a human mAb to DNA (16/6Id). Immunized mice develop Abs to the 16/6Id immunogen, DNA, and nuclear Ags. Subsequently, clinical manifestations of disease develop, including leukopenia, proteinuria, and immune complex deposits in the kidney. MHC class I Ags play a critical role in the induction of experimental SLE, as demonstrated by the finding that class I-deficient mice are resistant to disease induction. This finding suggested that agents that reduce MHC class I expression might mitigate experimental SLE in normal mice. These studies report that methimazole, which has been shown to repress class I transcription in some cell lines, reduces class I expression on PBLs in vivo and prevents the development of clinical manifestations of SLE in 16/6Id-immunized mice. These data suggest that methimazole, which has been used in the treatment of Graves' disease, may be useful in the clinical treatment of SLE and other autoimmune diseases.
Singer
D S
DS
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Kohn
L D
LD
Zinger
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H
Mozes
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E
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000276:immunology; D004247:DNA / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D007114:Immunization; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000517:prevention & control*; D008713:Methimazole / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D008713:Methimazole; D004247:DNA