Autoimmunity systemic lupus erythematosus-prone

BXSB/Mp, NZBxNZW/Fl, NZM, AKR). Experience with any of these strains is scarce and is restricted mainly to salts of heavy metals such as mercury. Mercury has been clearly shown to have immunostimulatory effects in NZBxNZW/Fl mice (Pollard et al., 1999). In a study examining the immunotoxic effects of diphenyl-hydantoin (Bloksma et al., 1994), MRL mice were exposed to the drug in the drinking-water for a period of six months in this case, however, no indications of adverse immune reactions were found. Future studies should include more autoimmunogenic pharmaceuticals and negative controls in order to determine the extent to which systemic lupus erythematosus-prone models are useful to study or predict chemical-induced autoimmunity. 

Keegan S, Nadwodny K, Speal B, Herzyk D, Soos J. Adaptation of the systemic lupus erythematosus prone (NZB X NZW)F1 mouse strain for autoimmune toxicology evaluation. The Toxicologist CD 84 S-1, Abstract 910,2005. 

Outcomes of in vitro methods or simple in vivo methods such as the PLNA, only indicate whether a compound can sensitize the immune system. They do not predict whether a compound can induce an autoimmune disease. For that disease models are warranted. However, most disease models, as mentioned, will often require predisposed animal strains such as systemic lupus erythematosus (SLE)-prone mice [81, 82]. Often models using autoimmune-prone mice or rats (including the BN rat) are considered too sensitive and are for that reason undesired by various stakeholders (i.e., pharmaceutical industries, regulatory agencies). 

Autoimmune responses seem to be the underlying basis for a number of diseases, including rheumatoid arthritis, diabetes mellitus, myasthenia gravis, systemic lupus erythematosus, scleroderma, polymyositis/der-matomyositis, and several other disorders.25,27,44 As indicated previously, it is not exactly clear what factors cause autoimmune responses, as well as why certain individuals are more prone to autoimmune-related diseases. Nonetheless, drugs that suppress the immune system can limit damage to various other tissues, and these drugs may produce dramatic improvements in patients with diseases that are caused by an autoimmune response. 

DNA vaccines are derived from bacterial DNA plasmid and, thus, are able to stimulate anti-DNA antibodies. If these antibodies are cross-reactive with host chromosomal DNA, they could act like autoantibodies and induce autoimmune diseases (such as systemic lupus erythematosus) characterized by the accumulation of DNA, antinuclear antibodies, and complement in various organs along with local inflammatory responses. Specific lupus-prone mouse strains exist that develop a similar disease. Repeated application of DNA vaccines to these mice did not alter the onset or the course of the disease. In normal mice, anti-DNA antibodies were induced by DNA vaccines, but these remained far below those levels... 

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