The impact of a new immunomodulator oxo-quinoline-3-carboxamide on the progression of experimental lupus

• Autoimmune, lupus-prone MRL lpr/lpr mice were treated orally with oxo-quinoline-3-carboxamide (ABR-25757), a newly developed immunomodulator. Treatment was initiated in one set of experiment at the age of 10 weeks, before the onset of clinically apparent disease, and in another set at 15 weeks, after the development of established lupus disease. Beneficial therapeutic effects were obtained even when ABR-25757 was administered at the lowest dose tested (7.5 microg/mouse/week) to 15 weeks old mice with established lupus disease. The effects of ABR-25757 on longevity, as well as on development of glomerulonephritis were pronounced and comparable with those of LS-2616, a potent immunomodulator. Administration of ABR-25757 did not significantly alter T cell responses in vivo nor in vitro. In addition, it only marginally suppressed B cell responses measured as frequencies of immunoglobulin secreting cells. By the same token this compound did not affect overall leukocyte content in primary (bone marrow) or secondary (spleen) lymphoid tissues. In contrast, treatment with ABR-25757 up regulated expression of pro-inflammatory transcription factors NF-kappaB and AP-1. These results suggest (a) a potential therapeutic role of ABR-25757 in the treatment of experimental lupus and (b) that the effect of the treatment is mediated by immunodeviation rather than by immunosuppression.

Nyckelord

Animals

Disease Models

Animal

Female

Immunity

Natural/drug effects

Immunoglobulins/immunology

Immunologic Factors/*therapeutic use

Lupus Erythematosus

Systemic/*drug therapy/immunology

Lymphocyte Activation/drug effects/immunology

Male

Mice

Mice

Inbred MRL lpr

Quinolones/*therapeutic use

T-Lymphocytes/drug effects/immunology

Transcription Factors/immunology

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