Mercury induces an unopposed inflammatory response in human peripheral blood mononuclear cells in vitro

Renee M. Gardner, Jennifer F. Nyland, Sean L. Evans, Susie B. Wang, Kathleen M. Doyle, Ciprian M. Crainiceanu, Ellen K. Silbergeld

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: The human immune response to mercury is not well characterized despite the body of evidence that suggests that Hg can modulate immune responses, including the induction of autoimmune disease in some mouse models. Dysregulation of cytokine signaling appears to play an important role in the etiology of Hg-induced autoimmunity in animal models. OBJECTIVES: In this study, we systematically investigated the human immune response to Hg in vitro in terms of cytokine release. METHODS: Human peripheral blood mononuclear cells (PBMCs) were isolated from 20 volunteers who donated blood six separate times. PBMCs were cultured with lipopolysaccharide and concentrations of mercuric chloride (HgCl2) up to 200 nM. Seven cytokines representing important pathways in physiologic and pathologic immune responses were measured in supernatants. We used multi level models to account for the intrinsic clustering in the cytokine data due to experimental design. RESULTS: We found a consistent increase in the release of the pro inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α, and concurrent decrease in release of the antiinflammatory cytokines interleukin 1-receptor antagonist (IL-1Ra) and IL-10 in human PBMCs treated with sub cytotoxic concentrations of HgCl2. IL-4, IL-17, and interferon-γ increased in a concentration - response manner. These results were replicated in a second, independently recruited population of 20 different volunteers. CONCLUSIONS: Low concentrations of HgCl2 affect immune function in human cells by dysregulation of cytokine signaling pathways, with the potential to influence diverse health outcomes such as susceptibility to infectious disease or risk of auto immunity.

Original languageEnglish (US)
Pages (from-to)1932-1938
Number of pages7
JournalEnvironmental health perspectives
Volume117
Issue number12
DOIs
StatePublished - Dec 2009

Keywords

  • Immunotoxicity
  • Inflammation
  • Mercury
  • Multilevel modeling

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Fingerprint Dive into the research topics of 'Mercury induces an unopposed inflammatory response in human peripheral blood mononuclear cells in vitro'. Together they form a unique fingerprint.

Cite this