Comparison of chlordecone effects on autoimmunity in (NZBxNZW) F(1) and BALB/c mice.
It has been shown previously that chronic treatment with relatively low doses of chlordecone accelerates the development of systemic lupus erythematosus (SLE) in ovariectomized female (NZBxNZW) F(1) mice. In this study, the effect of chronic chlordecone treatment on SLE was evaluated in ovary-intact female (NZBxNZW) F(1) mice, as well as in female mice from a strain that is not lupus-prone, BALB/c. Chlordecone was administered chronically via implanted sustained-release pellets, and mice were monitored over time for the appearance of elevated autoantibodies (anti-dsDNA and anti-chromatin) and for the development of renal impairment, both indicators of SLE. Chlordecone treatment in (NZBxNZW) F(1) mice shortened significantly the time to onset of elevated autoantibody titers and renal disease in a dose-related manner. The doses required to produce this effect were similar to those observed previously to accelerate SLE development in ovariectomized females. Treatment of female BALB/c mice with chlordecone for up to one year did not produce elevated autoantibody titers or renal disease, suggesting an inability of chlordecone to cause a break in tolerance in this strain. These observations confirm the ability of chronic chlordecone to influence SLE, but demonstrate the importance of genetic background for this effect.
Sobel
Eric S
ES
Department of Medicine, J. Hillis Miller Health Science Center, University of Florida, 1600 S.W. Archer Rd., Box 100221, Gainesville, FL 32610, USA. sobeles@medicine.ufl.edu
Wang
Fei
F
Butfiloski
Edward
E
Croker
Byron
B
Roberts
Stephen M
SM
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects*; D007631:Chlordecone / Q000008:administration & dosage / Q000633:toxicity*; D002843:Chromatin / Q000276:immunology; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D010052:Ovariectomy; D013045:Species Specificity
D000974:Antibodies, Antinuclear; D002843:Chromatin; D003692:Delayed-Action Preparations; D007074:Immunoglobulin G; D007306:Insecticides; D007631:Chlordecone