Study on Thimerosal and Immune System Dysfunction

[Guest guest]

I thought this study was interesting.

Sharon

FOR IMMEDIATE RELEASE:

March 21, 2006, 12:01 a.m. EST

CONTACT: Finney

(916) 734-9064

karen.finney@...

UC DAVIS STUDY WITH MICE LINKS THIMEROSAL WITH IMMUNE SYSTEM DYSFUNCTION

(Sacramento, Calif.) A team of cell biologists, toxicologists and molecular

bioscientists at the University of California, , 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 Ëœcommunicate' 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. In addition to being a direct neurotoxicant, the UC

study indicates that 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.

A copy of " Uncoupling of ATP-mediated Calcium Signaling and

Dysregulated IL-6 Secretion in Dendritic Cells by Nanomolar Thimerosal "

can be downloaded at http://www.ehponline.org/docs/2006/8881/abstract.html.

# # #

The NIEHS-funded Center for Children's Environmental Health and Disease

Prevention is a multi-disciplinary research organization established to examine

how toxic chemicals may influence the development of autism in children. The

center's goal is to contribute knowledge about autism that

will lead to new prevention and treatment strategies. For more information,

visit www.vetmed.ucdavis.edu/cceh. The UC M.I.N.D. (Medical

Investigation of Neurodevelopmental Disorders) Institute is a unique

collaborative

center bringing together parents, scientists, clinicians and educators for

research on autism and other neurodevelopmental disorders.

For more information, visit www.mindinstitute.org.