Skip to main content

Advertisement

Log in

Oral exposure to inorganic mercury alters T lymphocyte phenotypes and cytokine expression in BALB/c mice

  • Inorganic Compounds
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Mercury is a well-recognized health hazard and an environmental contaminant. Mercury modulates immune responses ranging from immune suppression to autoimmunity but the mechanisms responsible for these effects are still unclear. Male BALB/c mice were exposed continuously to 0, 0.3, 1.5, 7.5, or 37.5 ppm mercury in drinking water for 14 days. Body weight was reduced at the highest dose of mercury whereas the relative kidney and spleen weights were significantly increased. The dose range of mercury used did not cause hepatotoxicity as indicated by circulating alanine aminotransferase and aspartate aminotransferase levels. Circulating blood leukocytes were elevated in mice treated with the highest dose of mercury. Mercury ranging from 1.5 to 37.5 ppm dose-dependently decreased CD3+ T lymphocytes in spleen; both CD4+ and CD8+ single-positive lymphocyte populations were decreased. Exposure to 7.5 and 37.5 ppm mercury decreased the CD8+ T lymphocyte population in the thymus, whereas double-positive CD4+/CD8+ and CD4+ thymocytes were not altered. Mercury altered the expression of inflammatory cytokines (tumor necrosis factor α, interferon γ, and interleukin-12), c-myc, and major histocompatibility complex II, in various organs. Results indicated that a decrease in T lymphocyte populations in immune organs and altered cytokine gene expression may contribute to the immunotoxic effects of inorganic mercury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.

Similar content being viewed by others

References

  • Badou A, Savignac M, Moreau M, Leclerc C, Pasquier R, Druet P, Pelletier L (1997) HgCl2-induced interleukin-4 gene expression in T cells involves a protein kinase C-dependent calcium influx through L-type calcium channels. J Biol Chem 272:32411–32418

    Article  CAS  PubMed  Google Scholar 

  • Bigazzi PE (1998) Mercury. In: Zelikoff J, Thomas P (eds) Metal immunotoxicology. Taylor and Francis, London, pp 131–161

  • Blanck G (2002) Components of the IFNγ signaling pathway in tumorigenesis. Arch Immunol Ther Exp 50:151–158

    CAS  Google Scholar 

  • Cember H, Gallagher P, Faulkner A (1968) Distribution of mercury among blood fractions and serum proteins. Am Ind Hyg Assoc J 29:233–237

    CAS  PubMed  Google Scholar 

  • Christensen MM, Ellermann-Eriksen S, Rungby J, Mogensen SC (1996) Influence of mercuric chloride on resistance to generalized infection with herpes simplex virus type 2 in mice. Toxicology 114:57–66

    Article  CAS  PubMed  Google Scholar 

  • Gerstner HB, Huff JE (1977) Clinical toxicology of mercury. J Toxicol Environ Health 2:491–526

    PubMed  Google Scholar 

  • Godfrey DI, Kennedy J, Gately MK, Hakimi J, Hubbard BR, Zlotnik A (1994) IL-12 influences intrathymic T cell development. J Immunol 152:2729–2735

    CAS  PubMed  Google Scholar 

  • Hu H, Moller G, Abedi-Valugerdi M (1997) Major histocompatibility complex class II antigens are required for both cytokine production and proliferation induced by mercuric chloride in vitro. J Autoimmun 10:441–446

    Article  CAS  PubMed  Google Scholar 

  • Hultman P, Bell LJ, Enestrom S, Pollard KM (1992) Murine susceptibility to mercury. I. Autoantibody profiles and systemic immune deposits in inbred, congenic, and intra-H-2 recombinant strains. Clin Immunol Immunopathol 65:98–109

    CAS  PubMed  Google Scholar 

  • Hultman P, Bell LJ, Enestrom S, Pollard KM (1993) Murine susceptibility to mercury. II. Autoantibody profiles and renal immune deposits in hybrid, backcross, and H-2d congenic mice. Clin Immunol Immunopathol 68:9–20

    Article  CAS  PubMed  Google Scholar 

  • Jiang Y, Moller G (1995) In vitro effects of HgCl2 on murine lymphocytes. I. Preferable activation of CD4+ T cells in a responder strain. J Immunol 154:3138–3146

    CAS  PubMed  Google Scholar 

  • Johansson U, Sander B, Hultman P (1997) Effects of the murine genotype on T cell activation and cytokine production in murine mercury-induced autoimmunity. J Autoimmun 10:347–355

    Article  CAS  PubMed  Google Scholar 

  • Johnson VJ, Sharma RP (2001) Gender-dependent immunosuppression following subacute exposure to fumonisin B1. Int Immunopharmacol 1:2023–2034

    Article  CAS  PubMed  Google Scholar 

  • Kaiser J (2000) Mercury report backs strict rules. Science 289:371–372

    CAS  PubMed  Google Scholar 

  • Kim SH, Johnson VJ, Sharma RP (2002) Mercury inhibits nitric oxide production but activates proinflammatory cytokine expression in murine macrophage: differential modulation of NF-κB and p38 MAPK signaling pathways. Nitric Oxide 7:67–74

    Article  CAS  PubMed  Google Scholar 

  • Koller LD (1975) Methylmercury: effect on oncogenic and nononcogenic viruses in mice. Am J Vet Res 36:1501–1504

    CAS  PubMed  Google Scholar 

  • Koller LD (1980) Immunotoxicology of heavy metals. Int J Immunopharmacol 2:269–279

    Article  CAS  PubMed  Google Scholar 

  • Kosuda LL, Hannigan MO, Bigazzi PE, Leif JH, Greiner DL (1996) Thymus atrophy and changes in thymocyte subpopulations of BN rats with mercury-induced renal autoimmune disease. Autoimmunity 23:77–89

    CAS  PubMed  Google Scholar 

  • Kosuda LL, Whalen B, Greiner DL, Bigazzi PE (1998) Mercury-induced autoimmunity in Brown Norway rats: kinetics of changes in RT6+ T lymphocytes correlated with IgG isotypes of circulating autoantibodies to laminin 1. Toxicology 125:215–231

    Article  CAS  PubMed  Google Scholar 

  • Kunzmann S, Wohlfahrt JG, Itoh S, Asao H, Komada M, Akdis CA, Blaser K, Schmidt-Weber CB (2003) SARA and Hgs attenuate susceptibility to TGF-β1-mediated T cell suppression. FASEB J 17:194–202

    Article  CAS  PubMed  Google Scholar 

  • Locksley RM, Wakil AE, Corry DB, Pingel S, Bix M, Fowell DJ (1995) The development of effector T cell subsets in murine Leishmania major infection. Ciba Found Symp 195:110–117

    CAS  PubMed  Google Scholar 

  • Madrenas J, Parfrey NA, Halloran PF (1991) Interferon gamma-mediated renal MHC expression in mercuric chloride-induced glomerulonephritis. Kidney Int 39:273–281

    CAS  PubMed  Google Scholar 

  • National Toxicology Program (1993) Toxicology and carcinogenesis studies of mercuric chloride (CAS No. 7487-94-7) in F344/N rats and B6CF1 mice. NTP Technical Report 408. NIH publication 91-3139, US Department of Health and Human Services/Public Health Service/National Institutes of Health, Research Triangle Park NC

  • Nielsen JB, Andersen O (1989) Oral mercuric chloride exposure in mice: effects of dose on intestinal absorption and relative organ distribution. Toxicology 59:1–10

    Article  CAS  PubMed  Google Scholar 

  • Nielsen JB, Andersen O (1990) Disposition and retention of mercuric chloride in mice after oral and parenteral administration. J Toxicol Environ Health 30:167–180

    CAS  PubMed  Google Scholar 

  • Perlingeiro RC, Queiroz ML (1994) Polymorphonuclear phagocytosis and killing in workers exposed to inorganic mercury. Int J Immunopharmacol 16:1011–1017

    Article  CAS  PubMed  Google Scholar 

  • Pietsch P, Vohr HW, Degitz K, Gleichmann E (1989) Immunological alterations inducible by mercury compounds. II. HgCl2 and gold sodium thiomalate enhance serum IgE and IgG concentrations in susceptible mouse strains. Int Arch Allergy Appl Immunol 90:47–53

    CAS  PubMed  Google Scholar 

  • Pollard KM, Hultman P (1997) Effects of mercury on the immune system. Met Ions Biol Syst 34:421–440

    CAS  PubMed  Google Scholar 

  • Prouvost-Danon A, Abadie A, Sapin C, Bazin H, Druet P (1981) Induction of IgE synthesis and potentiation of anti-ovalbumin IgE antibody response by HgCl2 in the rat. J Immunol 126:699–792

    CAS  PubMed  Google Scholar 

  • Reardon CL, Lucas DO (1987) Heavy-metal mitogenesis: Zn++ and Hg++ induce cellular cytotoxicity and interferon production in murine T lymphocytes. Immunobiology 175:455–469

    CAS  PubMed  Google Scholar 

  • Rosloniec EF, Latham K, Guedez YB (2002) Paradoxical role of IFNγ in models of Th1-mediated autoimmunity. Arthritis Res 4:333–336

    Article  PubMed  Google Scholar 

  • Sapin C, Druet E, Druet P (1977) Induction of anti-glomerular basement membrane antibodies in the Brown-Norway rat by mercuric chloride. Clin Exp Immunol 28:173–179

    CAS  PubMed  Google Scholar 

  • Shen X, Lee K, Konig R (2001) Effects of heavy metal ions on resting and antigen-activated CD4+ T cells. Toxicology 169:67–80

    Article  CAS  PubMed  Google Scholar 

  • Shenker BJ, Rooney C, Vitale L, Shapiro IM (1992) Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. I. Suppression of T-cell activation. Immunopharmacol Immunotoxicol 14:539–553

    CAS  PubMed  Google Scholar 

  • Trinchieri G (2003) Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3:133–146

    Article  CAS  PubMed  Google Scholar 

  • Tsunoda M, Sharma RP (1999) Modulation of tumor necrosis factor α expression in mouse brain after exposure to aluminum in drinking water. Arch Toxicol 73:419–426

    Article  CAS  PubMed  Google Scholar 

  • Vamvakas S, Bittner D, Koster U (1993) Enhanced expression of the protooncogenes c-myc and c-fos in normal and malignant renal growth. Toxicol Lett 67:161–172

    Article  CAS  PubMed  Google Scholar 

  • Wild LG, Ortega HG, Lopez M, Salvaggio JE (1997) Immune system alteration in the rat after indirect exposure to methyl mercury chloride or methyl mercury sulfide. Environ Res 74:34–42

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported in part by the Center of Academic Excellence in Toxicology at the University of Georgia and the Fred C. Davison Endowment Fund. The experiments employed in this work complied with the current laws of the United States of America.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Raghubir P. Sharma.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, S.H., Johnson, V.J. & Sharma, R.P. Oral exposure to inorganic mercury alters T lymphocyte phenotypes and cytokine expression in BALB/c mice. Arch Toxicol 77, 613–620 (2003). https://doi.org/10.1007/s00204-003-0497-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-003-0497-0

Keywords

Navigation