|MedPage Today Action Points
- Explain to interested patients that this study
suggests that thimerosal can interfere with the
cell-signaling and development of dendritic cells,
key immune system cells that activate T-cells as
part of the immune response.
- Caution patients that this study does not
purport to show any link between the presence of
thimerosal in vaccines and the development of autism
or other developmental disorders.
DAVIS, Calif., March 21 - Thimerosal, a mercury-containing
organic no longer used as a preservative in many pediatric
vaccines, can disrupt certain antigen presenting cells and may
affect the immune response to external factors, reported
Although far from the smoking gun that proponents of a
thimerosal-autism link seek, the finding suggested that
thimerosal exposure could cause dendritic cells to activate
"aberrant and harmful immune responses," according to Isaac N.
Pessah, Ph.D., and colleagues of the University of California at
Davis. They reported the research online in Environmental Health
"This is the first time that thimerosal has been shown to
selectively alter the normal functions of dendritic cells," said
Dr. Pessah, a toxicologist and director of the Children's Center
for Environmental Health and Disease Prevention at Cal Davis.
He added that dendritic cells "play pivotal roles in
overcoming viral and bacterial invaders by coordinating the
immune system's overall combat response."
Yet, Dr. Pessah emphasized, "Our findings do not directly
implicate thimerosal as a single causative agent for triggering
neurodevelopmental disorders such as autism."
"There is growing evidence that autism is several disorders
that we now refer to as just one," he added. "There is also
growing evidence that some children with autism have unique
immune cell composition and responses to antigens. The results
of our work provide a framework to test the hypothesis that the
genetic background of some individuals may render them
especially susceptible to thimerosal."
Dendritic cells are antigen-presenting cells that are potent
activators of T-cells. But as Dr. Pessah and colleagues
demonstrated in their study of cultured mouse cells, exposure to
thimerosal disrupts calcium-channel signaling within dendritic
cells, thereby altering growth patterns, maturation, and
They determined this by exposing both mature and immature
dendritic cells cultured from murine bone marrow to thimerosal
at varying concentrations. The authors used
immunocytofluorescence to visualize the effect of thimerosal
exposure on calcium channels. Thimerosal contains approximately
50% ethylmercury by weight.
They found that at concentrations of 20 parts per billion,
exposure of the dendritic cells to thimerosal altered the normal
cross-talk between the calcium channels RyR12 and IP3R1, thereby
"garbling the normal signaling system between them."
In addition, exposure to the compound resulted in irregular
secretion by the dendritic cells of the pro-inflammatory
When they ramped up thimerosal concentrations to 200 parts
per billion, they found that it induced apoptosis of dendritic
cells before they had fully matured, thereby preventing T-cell
The finding suggests that in addition to its known neurotoxic
properties, ethylmercury may also be an immunotoxicant, the
"A practical implication of the present findings has
relevance to the commercial uses of thimerosal as an
antimicrobial agent in vaccines and consumer products since they
identify dendritic cells as sensitive targets for thimerosal and
ethylmercury-mediated dysfunction," they wrote. "Given the
importance of dendritic cells as a front line in regulating
lymphocyte mediated immunity and tolerance, altering dendritic
cell functions by forms of ethylmercury should be considered
when assessing contributions to altered immune function."
They stopped short, however, of fingering thimerosal as a
cause of autism. Thimerosal is still used in some commercial
Other experts also advised drawing no final conclusions
regarding thimerosal and autism on the basis of on this
"These findings should be interpreted cautiously. Although
they suggest that thimerosal may affect dendritic cell function,
the pathophysiological consequences of thimerosal remain
unclear," said David A. Schwartz, M.D., director of the National
Institute of Environmental Health Sciences, who was not involved
in the study.
Primary source: Environmental Health Perspectives
Goth SR et al.
Uncoupling of ATP-mediated Calcium Signaling and Dysregulated
IL-6 Secretion in Dendritic Cells by Nanomolar Thimerosal
Environmental Health Perspectives. doi:10.1289/ehp.8881