Assessment of autoimmunity-inducing potential using the brown Norway rat challenge model.
The development of autoimmune disease in humans is thought to occur as a result of the interactions of a genetic predisposition of the host and environmental factors. There is evidence that treatment with certain drugs and exposure to environmental toxicants increase the risk associated with the development and severity of autoimmune disease. When exposed to certain chemicals, Brown Norway (BN) rats develop autoimmune disease similar to human systemic lupus erythematosus (SLE) characterized by elevation of antibody levels to self and non-self antigens which can result in the formation of immune complexes and lead to a fatal glomerulonephritis. A unique characteristic of the BN rat model is that the increase in IgE is self-limiting with levels eventually returning to normal. The objective of these studies was to determine if the BN rat and the self-limiting nature of the IgE response could be used in identifying compounds capable of initiating autoimmune responses. Two compounds known to produce autoimmunity, mercuric chloride and D-penicillamine, were studied as were, trichloroethylene and silicone gel, two agents suspected of inducing autoimmune disease. The results indicated that the BN rat model may prove useful for detecting compounds with the potential to produce autoimmunity, particularly if a HgCl(2) challenge is incorporated into the evaluation.
White
K L
KL
Department of Pharmacology and Toxicology, Medical College of Virginia Campus/Virginia Commonwealth University, Richmond, VA, USA. kwhite@hsc.vcu.edu
David
D W
DW
Butterworth
L F
LF
Klykken
P C
PC
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000633:toxicity*; D000917:Antibody Formation; D000931:Antidotes / Q000633:toxicity*; D001327:Autoimmune Diseases / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D008627:Mercuric Chloride / Q000633:toxicity*; D010396:Penicillamine / Q000633:toxicity*; D051381:Rats; D011914:Rats, Inbred BN; D020034:Silicone Gels / Q000633:toxicity; D012997:Solvents / Q000633:toxicity; D014241:Trichloroethylene / Q000633:toxicity
D000891:Anti-Infective Agents, Local; D000931:Antidotes; D020034:Silicone Gels; D012997:Solvents; D014241:Trichloroethylene; D007073:Immunoglobulin E; D008627:Mercuric Chloride; D010396:Penicillamine