UC study with mice links thimerosal with immune system dysfunction

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study with mice links thimerosal with immune system dysfunction

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22.03.2006

A team of cell biologists, toxicologists and molecular

bioscientists at UC has published a study connecting thimerosal with

disruptions in antigen-presenting cells known as dendritic cells obtained from

mice. The study provides the first evidence that dendritic cells show unprecedented

sensitivity to thimerosal, resulting in fundamental changes in the immune

system’s ability to respond to external factors. The study was published

online today and will be available in the July print edition of Environmental

Health Perspectives, the peer-reviewed scientific publication of the National

Institute of Environmental Health Sciences.

" This is the first time that thimerosal has been shown to selectively

alter the normal functions of dendritic cells, " said Isaac Pessah, a

toxicologist with the UC School of Veterinary Medicine, director of the

Children’s Center for Environmental Health and Disease Prevention and

senior author of the study. " Dendritic cells play pivotal roles in

overcoming viral and bacterial invaders by coordinating the immune

system’s overall combat response. " One dendritic cell can activate

as many as 300 T-cells – white blood cells that help find and kill

external agents that attack the immune system – making them the most

effective immune system activators.

The study shows how intricate connections between calcium channels in dendritic

cells change when exposed to thimerosal.

" The slightest fluctuation in how calcium channels

’communicate’ can alter the growth, maturation and activation of

dendritic cells, " explained Pessah. " Thimerosal dramatically alters

how two key calcium channels, code-named RyR1 and IP3R1, found in dendritic

cells function as a team by ’garbling’ the normal signaling system

between them. "

When thimerosal, at a concentration as low as 20 parts per billion, alters the

fidelity of normal calcium signals, dendritic cells show abnormal secretion of

IL-6 cytokine – a potent chemical signal that initiates inflammatory

responses. Higher concentrations – 200 parts per billion – causes

programmed death of dendritic cells, preventing them from maturing and doing

their primary job of activating T-cells. Without proper feedback to guide its

response, a normal dendritic cell can quickly become " a rogue, producing

misinformation that could activate aberrant and harmful immune responses, "

Pessah explained. " Even one rogue dendritic cell can activate many

inappropriate immune responses. "

The research team conducted the study on cells cultured from a strain of mouse

not particularly susceptible to immune dysregulation. Using fluorescent stains

and powerful microscopes to study both immature and mature dendritic cells from

bone marrow cultured under normal physiological conditions, the researchers

discovered that extremely small levels of thimerosal interfere significantly

with calcium channel function after just a few minutes of exposure. They also

observed that immature dendritic cells are particularly sensitive to

thimerosal.

Thimerosal is a cheap and effective mercury-based preservative. Its potential

effects on embryonic neuron development led to its removal from many pediatric

vaccines. However, it is still used in influenza, diphtheria and tetanus

vaccines, blood products and many over-the-counter pharmaceuticals. The

concentrations of thimerosal used by the UC researchers were comparable

to those attained in childhood vaccinations containing the preservative.

Researchers and parents have previously proposed links between childhood

vaccines and autism, a neurodevelopmental disorder that affects language skills

and social interactions. The UC study indicates that in addition to being

a direct neurotoxicant, thimerosal may also be an immunotoxicant, leaving the

immune system vulnerable to microbes and other external influences.

" Our findings do not directly implicate thimerosal as a single causative

agent for triggering neurodevelopmental disorders such as autism, " Pessah

said. " There is growing evidence that autism is several disorders that we

now refer to as just one. 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. "

Other experts also advise drawing no final conclusions regarding thimerosal and

autism based on these outcomes.

" These findings should be interpreted cautiously. Although they suggest

that thimerosal may affect dendritic cell function, the pathophysiological

consequences of thimerosal remain unclear, " said A. Schwartz, a

physician and director of the National Institute of Environmental Health

Sciences.

Since cell functions can differ across organisms, Pessah will next study dendritic

cells isolated from the blood of children with and without autism to confirm if

the intercellular changes are the same in humans. The initial mouse study was

funded by the National Institute of Environmental Health Sciences and the UC

M.I.N.D. Institute. Joining Pessah on the scientific team were molecular

bioscientists R. Goth, Ruth A. Chu and Gennady Cherednichenko and

pathologist P. Gregg.

Finney | Source: EurekAlert!

Further information: www.ucdmc.ucdavis.edu

www.ehponline.org/docs/2006/8881/abstract.html

www.mindinstitute.org

http://www.innovations-report.com/html/reports/life_sciences/report-57003.html