Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Immunosuppressive and autoimmune effects of thimerosal in mice

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Havarinasab, S.
  • Haggqvist, B.
  • Bjorn, E.
  • Pollard, Kenneth Michael
  • Hultman, P.

publication date

  • April 2005

journal

  • Toxicology and Applied Pharmacology  Journal

abstract

  • The possible health effects of the organic mercury compound thimerosal (ethylmercurithiosalicylate), which is rapidly metabolized to ethylmercury (EtHg), have recently been much debated and the effect of this compound on the immune system is largely unknown. We therefore studied the effect of thimerosal by treating A.SW (H-2s) mice, susceptible to induction of autoimmunity by heavy metals, with 10 mg thimerosal/L drinking water (internal dose ca 590 microg Hg/kg body weight/day) for up to 30 days. The lymph node expression of IL-2 and IL-15 mRNA was increased after 2 days, and of IL-4 and IFN-gamma mRNA after 6 and 14 days. During the first 14 days treatment, the number of splenocytes, including T and B cells as well as Ig-secreting cells decreased. A strong immunostimulation superseded after 30 days treatment with increase in splenic weight, number of splenocytes including T and B cells and Ig-secreting cells, and Th2- as well as Th-1-dependent serum immunoglobulins. Antinucleolar antibodies (ANoA) targeting the 34-kDa nucleolar protein fibrillarin, and systemic immune-complex deposits developed. The H-2s strains SJL and B10.S also responded to thimerosal treatment with ANoA. The A.TL and B10.TL strain, sharing background genes with the A.SW and B10.S strain, respectively, but with a different H-2 haplotype (t1), did not develop ANoA, linking the susceptibility to H-2. Thimerosal-treated H-2s mice homozygous for the nu mutation (SJL-nu/nu), or lacking the T-cell co-stimulatory molecule CD28 (B10.S-CD28-/-), did not develop ANoA, which showed that the autoimmune response is T-cell dependent. Using H-2s strains with targeted mutations, we found that IFN-gamma and IL-6, but not IL-4, is important for induction of ANoA by thimerosal. The maximum added renal concentration of thimerosal (EtHg) and inorganic mercury occurred after 14 days treatment and was 81 microg Hg/g. EtHg made up 59% and inorganic mercury 41% of the renal mercury. In conclusion, the organic mercury compound thimerosal (EtHg) has initial immunosuppressive effects similar to those of MeHg. However, in contrast to MeHg, thimerosal treatment leads in genetically susceptible mice to a second phase with strong immunostimulation and autoimmunity, which is T-cell dependent, H-2 linked and may at least partly be due to the inorganic mercury derived from the metabolism of ethyl mercury.

subject areas

  • Administration, Oral
  • Animals
  • Antibodies, Antinuclear
  • Antigens, CD80
  • Autoimmunity
  • B-Lymphocytes
  • Blood Vessels
  • CD4-Positive T-Lymphocytes
  • Cell Communication
  • Cell Proliferation
  • Female
  • Gene Expression
  • Immunoglobulin G
  • Immunoglobulin Light Chains
  • Immunosuppressive Agents
  • Interferon-gamma
  • Interleukin-4
  • Kidney
  • Leukocytes, Mononuclear
  • Lymph Nodes
  • Lymphocyte Activation
  • Male
  • Mesentery
  • Mice
  • Mice, Transgenic
  • Mutagenesis, Site-Directed
  • Mutation
  • Organ Size
  • RNA, Messenger
  • Receptors, Cytokine
  • Spleen
  • Thimerosal
scroll to property group menus

Research

keywords

  • autoimmunity
  • ethylmercury
  • immunosuppression
  • mice
  • thimerosal
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0041-008X

Digital Object Identifier (DOI)

  • 10.1016/j.taap.2004.08.019

PubMed ID

  • 15808517
scroll to property group menus

Additional Document Info

start page

  • 109

end page

  • 121

volume

  • 204

issue

  • 2

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support