The effects of CP 17193, an immunosuppressive pyrazaloquinoline, on the development of spontaneous lupus disease in NZBW F1 hybrid mice.
The effects of the immunosuppressive agent CP 17193 on the development of spontaneous lupus disease in female NZBW F1 hybrid mice were investigated. Long term dosing with CP 17193 markedly delayed the onset of mortality but did not extend the long term survival of the mice. CP 17193 significantly inhibited immune complex deposition in the glomeruli of 30- and 35-week-old mice and also reduced the levels of proteinuria in the 35-week-old mice. There was a slight reduction in the levels of circulating antinuclear antibody to ds DNA in CP 17193-treated mice but this was not statistically significant. Studies on immune cell function of 35-week-old mice dosed with CP 17193 showed significant reduction in the total numbers of spontaneous polyclonal antibody producing cells. Analysis of the results revealed these effects to result from a marked reduction in total spleen cell numbers in CP 17193-treated mice. When results were expressed as activity per cell unit the differences between drug-treated and control mice were small. Spleen cells from mice given a shorter dosing schedule of 7 weeks with CP 17193 showed an augmentation of IL-2 production and responsiveness. These results show CP 17193 having interesting selective immunomodulating activity on the immunopathogenesis of spontaneous murine lupus disease. Furthermore, compounds with this profile of activity may have a potential role in the treatment of some autoimmune diseases.
Bundick
R V
RV
Department of Biochemistry, Fisons plc, Research and Development Laboratories, Loughborough, UK.
Eady
R P
RP
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D001327:Autoimmune Diseases / Q000517:prevention & control*; D005260:Female; D005921:Glomerulonephritis / Q000517:prevention & control; D006824:Hybridization, Genetic; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D007668:Kidney / Q000473:pathology; D008177:Lupus Vulgaris / Q000517:prevention & control*; D051379:Mice; D008814:Mice, Inbred NZB; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D013154:Spleen / Q000276:immunology
D000974:Antibodies, Antinuclear; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D011720:Pyrazoles; C031793:CP 17193