Diethyldithiocarbamate, a novel immunomodulator, prolongs survival in autoimmune MRL-lpr/lpr mice.
MRL-lpr/lpr mice die at an early age from a spontaneously developing systemic lupus erythematosus-like disease and are characterized by massive lymphadenopathy, hyperproliferation of Lyt-2/L3T4 (null) T cells, decreased responses to mitogens, thymic atrophy, and very high serum autoantibody levels. Diethyldithiocarbamate (DTC), an immunomodulator suggested to enhance T cells, was used to treat 12-week-old female MRL-lpr/lpr mice (25 mg/kg/week). DTC treatment significantly prolonged survival (50% mortality, 43 weeks vs 20 weeks). Increased survival was associated with decreased lymphadenopathy, decreased proliferation of null cells, restoration of impaired mitogen responses, decreased thymic atrophy, and decreased serum levels of anti-DNA and anti-histone antibodies. Studies of cell surface antigen phenotype demonstrated increased expression of Lyt-2 and macrophage surface antigens. No effect on L3T4 single staining cells was observed. These results show that DTC significantly alters the disease course in these mice and suggest that DTC may be a useful treatment for autoimmune disease.
Halpern
M D
MD
Department of Microbiology and Immunology, University of Arizona, Tucson 85724.
Hersh
E
E
Yocum
D E
DE
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000401:mortality*; D004050:Ditiocarb / Q000627:therapeutic use*; D005260:Female; D007958:Leukocyte Count; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D013601:T-Lymphocytes / Q000166:cytology
D000276:Adjuvants, Immunologic; D000954:Antigens, Surface; D004050:Ditiocarb