Immunomodulation by mercuric chloridein vitro: application of different cell activation pathways
Open Access
- 14 February 2007
- journal article
- Published by Oxford University Press (OUP) in Clinical and Experimental Immunology
- Vol. 148 (2), 325-337
- https://doi.org/10.1111/j.1365-2249.2007.03338.x
Abstract
Evidence is emerging that exposure to mercury (Hg) may elicit many pathological manifestations, including immunomodulation. We tested whether changing cellular activation pathways may affect the immunomodulation by Hg. Human cell cultures were set up where isolated peripheral blood mononuclear cells, activated by monoclonal antibodies (MoAb: anti-CD3/-CD28/-CD40) or heat-killed Salmonella enterica serovar Enteritidis (hk-SE), exposed to mercuric chloride (HgCl2) for 24 h. Cell vitality was assessed by MTT assay, and modulation of cytokine profiles were monitored by enzyme-linked immunosorbent assay (ELISA), intracellular cytokine staining and reverse transcription–polymerase chain reaction (RT–PCR). Results show that Hg doses above 15 ng/ml significantly reduced cell vitality (P < 0·05). Lower doses elicited distinct effects on T helper 1 (Th1) and Th2 cytokine expression depending on cellular activation pathways. In MoAb-stimulated cells, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and interleukin (IL)-6 production was reduced. Doses up to 0·150 and 0·5 µg/ml increased IL-10 and IL-4 production, respectively, resulting in significantly reduced Th1/Th2 ratios. Stimulation by hk-SE, however, elevated Th1/Th2 ratios due to induction of IFN-γversus IL-10 production. Taken together, we conclude that low-level exposure to Hg, in the absence of inflammation, polarizes the immune response toward Th2, but not in the case of Th1-polarized responses elicited by Salmonella antigens that can be promoted instead. This demonstrates differential in vitro effects of Hg on the Th1/Th2 balance produced by different stimuli, which may have important experimental and scientific implications.This publication has 82 references indexed in Scilit:
- Systemically induced allergic exanthem from mercuryContact Dermatitis, 2004
- Susceptibility of Metallothionein-Null Mice to the Behavioral Alterations Caused by Exposure to Mercury Vapor at Human-Relevant ConcentrationToxicological Sciences, 2004
- Review: Environmental exposure to mercury and its toxicopathologic implications for public healthEnvironmental Toxicology and Water Quality, 2003
- The expanding universe of T-cell subsets: Th1, Th2 and moreImmunology Today, 1996
- Systemic Autoimmunity Due to Mercury Vapor Exposure in Genetically Susceptible Mice: Dose-Response StudiesToxicology and Applied Pharmacology, 1995
- Cytotoxicity and accumulation of Hg, Ag, Cd, Cu, Pb and Zn in human peripheral T and B lymphocytes and monocytes In VitroGeneral Pharmacology: The Vascular System, 1994
- Metallothionein induction in human peripheral blood lymphocytes by heavy metalsChemico-Biological Interactions, 1991
- The role of IL-10 in crossregulation of TH1 and TH2 responsesImmunology Today, 1991
- Human TH1 and TH2 subsets: doubt no moreImmunology Today, 1991
- TH2 cells in systemic autoimmunity: insights from allogeneic diseases and chemically-induced autoimmunityImmunology Today, 1991