Drinking water exposure to cadmium, an environmental contaminant, results in the exacerbation of autoimmune disease in the murine model

• Published in: Toxicology (Amsterdam) 2003-06, Vol.188 (2), p.233-250
• Main Authors: Leffel, Elizabeth K., Wolf, Carl, Poklis, Alphonse, White, Kimber L.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Antinuclear - biosynthesis; Antibodies, Antinuclear - blood; Antibodies, Antinuclear - immunology; Antigen-Antibody Complex - immunology; Antigen-Antibody Complex - metabolism; Antinuclear antibodies; Autoimmune Diseases - chemically induced; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; Autoimmune Diseases - metabolism; Autoimmunity; Biological and medical sciences; Body Weight; Cadmium - immunology; Cadmium - pharmacokinetics; Cadmium - toxicity; Cadmium exposure; Chemical and industrial products toxicology. Toxic occupational diseases; Disease Models, Animal; Drinking water; Environmental cadmium; Environmental Exposure - adverse effects; Female; Genetic Predisposition to Disease; Hypergammaglobulinemia - chemically induced; Hypergammaglobulinemia - immunology; Hypergammaglobulinemia - metabolism; Immunoglobulin Isotypes - immunology; Kidney - metabolism; Liver - metabolism; Medical sciences; Metals and various inorganic compounds; Mice; Mice, Inbred NZB; NZBW mouse; Organ Size; Random Allocation; Toxicology; Water Pollutants, Chemical - immunology; Water Pollutants, Chemical - pharmacokinetics; Water Pollutants, Chemical - toxicity
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(03)00092-1

Cadmium is a pervasive environmental contaminant. The primary route of exposure to the general population occurs via contaminated drinking water or food supplies. Our hypothesis was that cadmium could be a trigger for inducing autoimmune disease (AD) in genetically predisposed populations. Therefore, New Zealand Black/White F1 (NZBW) mice were exposed to cadmium via drinking water. Mice were exposed to: 0, 3, 30, 3000 or 10 000 parts per billion (ppb) of cadmium in tap water for 2, 4, 28, or 31 weeks. After 4 weeks of exposure, in the group of mice exposed to 10 000 ppb cadmium, there was an increased incidence of antinuclear antibodies (ANA). There was also deposition of immune complexes in all groups after 4 weeks of exposure. After 31 weeks, there were increases in IgG2a in mice exposed to low doses of cadmium. In an attempt to establish the progression from an autoimmune reaction to the development of AD, the biological marker for AD, proteinuria, was assessed. Onset of proteinuria was exacerbated by 11 weeks in mice exposed to cadmium. This data suggests that short-term exposure may result in a type of autoimmune reaction since the mice are beginning to produce ANA after only 4 weeks of exposure and there is immune-complex deposition in the kidney. Long-term exposure to cadmium appears to result in the exacerbation of AD as indicated by the development of proteinuria and continued presence of immune complexes in the kidney. The mechanism may involve the increased production of IgG2a, which is capable of forming immune complexes and causing autoimmune glomerulonephritis.