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 re sult of the interactions of a genetic predisposition of the host and enviro nmental factors. There is evidence that treatment with certain drugs and ex posure to environmental toxicants increase the risk associated with the dev elopment and severity of autoimmune disease. When exposed to certain chemic als, Brown Norway (BN) rats develop autoimmune disease similar to human sys temic lupus erythematosus (SLE) characterized by elevation of antibody leve ls to self and non-self antigens which can result in the formation of immun e 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 leve ls eventually returning to normal. The objective of these studies was to de termine if the BN rat and the self-limiting nature of the IgE response coul d be used in identifying compounds capable of initiating autoimmune respons es. Two compounds known to produce autoimmunity, mercuric chloride and D-pe nicillamine, 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 potenti al to produce autoimmunity, particularly if a HgCl2 challenge is incorporat ed into the evaluation. (C) 2000 Elsevier Science Ireland Ltd. All rights r eserved.