Immunomodulation by mercuric chloride in vitro: application of
different cell activation pathways.Hemdan NY, Lehmann I, Wichmann G,
Lehmann J, Emmrich F, Sack U.
Institute of Clinical Immunology and Transfusion Medicine (IKIT),
University of Leipzig, Germany. hemdan.nasr@[EMAIL PROTECTED]
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 *****sed 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)-gamma, tumour necrosis factor (TNF)-
alpha and interleukin (IL)-6 production was reduced. Doses up to 0.150
and 0.5 microg/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-gamma
versus 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 im****tant
experimental and scientific implications.
PMID: 17302730 [PubMed - in process]
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