Oral exposure to inorganic mercury alters T-lymphocyte phenotypes and cytokine gene expression in BALB/C Mice.
Kim-SH; Johnson-VJ; Sharma-RP
Toxicologist 2003 Mar; 72(S-1):14
Mercury is a well recognized health hazard and an environmental contaminant. Mercury is known to suppress immune responses, but the mechanisms responsible for this effect are still unclear. The aims of this study were to investigate the effect of mercury on immune parameters, such as hematology, lymphocyte phenotypes and cytokine gene expression. Male BALB/c mice were exposed continuously to 0, 0.3, 1.5, 7.5, or 37.5 ppm of mercury in drinking water for 14 days. Food and water consumption decreased in a dose-dependent manner in mice exposed to mercury. Body weight was reduced at the highest dose of mercury whereas the relative kidney and spleen weight were significantly increased. The dose-range of mercury used did not cause hepatotoxicity as indicated by circulating alanine aminotransferase and aspartate aminotransferase. Circulating blood leukocytes were elevated in mice treated with the highest dose of mercury. Single-cell splenocyte cultures were used to determine the effects of mercury treatment on mitogen-induced lymphocyte blastogenesis. Mercury at 1.5 ppm increased the PHA and LPS stimulation indices for T and B lymphocytes, respectively reflecting the observed decrease in basal splenocyte proliferation in mercury-treated mice. Exposure to 7.5 and 37.5 ppm of mercury decreased the CD8+ T lymphocyte population in thymus, whereas double positive CD4+/CD8+ and CD4+ thymocytes were not altered. Mercury ranging from 1.5 to 37.5 ppm dose-dependently decreased CD3+ T lymphocytes in spleen; both CD4+ and CD8+ single positive lymphocyte numbers were decreased. The population of CD45+ B lymphocytes was not changed. Mercury altered the expression of cytokines (tumor necrosis factor alpha;, interferon gamma;, interleukin-12), c-myc, and major histocompatibility complex II in various organs. Results indicated that decreases in T lymphocyte populations in immune organs and altered cytokine gene expression may contribute to the immunosuppressive effects of inorganic mercury.
Mercury-compounds; Mercury-poisoning; Immune-system-disorders; Heavy-metals; Heavy-metal-poisoning; Hematopoietic-system; Laboratory-animals; Animal-studies
The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah