Age and lpr dependent induction of increased sensitivity to the toxic effects of lipopolysaccharide and indomethacin in MRL mice: evidence for RES activation during disease progression.
Injection of 4.5-6 month old female MRL-lpr/lpr mice with 200-250 micrograms lipopolysaccharide led to the death of the animals within two days. Treatment of age matched female control mice (MRL-+/+) or young (3 month) MRL-lpr/lpr mice did not lead to similar toxicity. However, pretreatment of young mice with the pyridine extract of residue of Corynebacterium parvum (alternatively designated Propionibacterium acnes) prior to lipopolysaccharide injection, led to the rapid death of 100% of the mice. Similarly, treatment of old MRL-lpr/lpr mice, or young mice pretreated with the C. parvum extract, with doses of indomethacin non-toxic to MRL-+/+ mice (5 mg/kg), led to 100% mortality. These results indicate that the presence of the lpr gene in MRL mice leads to an age-dependent induction of RES activation. Whether this RES activation is a result of the autoimmune diseases these animals exhibit or is a secondary sequelae of the lymphoproliferation associated with the lpr gene cannot be ascertained. However, the finding of increased sensitivity of old MRL-lpr/lpr mice to the toxic effects of indomethacin indicates that the RES activation occurring in these animals is similar to that observed previously in mice bearing the BCL1-leukemia or treated with C. parvum.
Hart
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Joint Injury and Diseases Research Group, University of Calgary Health Sciences Centre, Alberta, Canada.
D000367:Age Factors; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D005260:Female; D007213:Indomethacin / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D012157:Mononuclear Phagocyte System / Q000187:drug effects* / Q000276:immunology
D008070:Lipopolysaccharides; D007213:Indomethacin