SSRIs and the immune system

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From Jan 22, 2006

Subject: Antidepressants May Also Affect Immune System

Commonly Used Antidepressants May Also Affect Human Immune System

Drugs that treat depression by manipulating the neurotransmitter

serotonin in the brain may also affect the user's immune system in ways

that are not yet understood, say scientists from town University

Medical Center and a Canadian research institute.

That's because the investigators found, for the first time, that

serotonin is passed between key cells in the immune system, and that the

chemical is specifically used to activate an immune response. They do

not know yet, however, whether these SSRI (selective serotonin reuptake

inhibitors) drugs " including the brands Prozac, Zoloft, Paxil and

others " could have either a beneficial or a damaging effect on human

immunity.

" The wider health implication is that commonly used SSRI

antidepressants, which target the uptake of serotonin into neurons, may

also impact the uptake in immune cells, " said Gerard Ahern, Ph.D.,

assistant professor of Pharmacology at town and lead researcher on

the study.

He said that while it may be possible that SSRI drugs may restore a

healthy immune function in people who are depressed and prone to

infections, it is possible that they might also bolster immunity to the

point that they trigger autoimmune disease. " At this point we just don't

know how these drugs might affect immunity, so we really need to clarify

the normal role of serotonin in immune cell functioning, " Ahern said.

The surprising finding that serotonin is rapidly passed between immune

cells in a manner similar to its transmission between brain neurons was

revealed in mid-October, when the research team published the findings

in the journal Blood. In December, the discovery was highlighted for the

general scientific audience by the journal Nature Reviews Immunology,

and now the research team is working to produce an animal model that may

help describe the precise nature of this interaction.

" The novelty is that we reveal a potential communication, involving the

transmitter serotonin, between immune cells that is normally only found

between neurons, " Ahern said.

In addition to Ahern, Peta Connell, Ph.D., from the Robarts Research

Institute in Canada, was also a co-lead researcher on the study.

Scientists from the Robarts Research Institute also contributed to the

work.

In the brain, serotonin transmission between neurons is associated with

feelings of pleasure, mood, and appetite, and the class of

antidepressants known as SSRIs keeps serotonin active within the

synaptic spaces between neurons, enhancing the chemical's positive

effects. Unlike in the brain, which uses chemical messengers to

communicate between nerve cells, the immune system is believed to

" converse " through physical contact -- one type of immune cell touches

another, setting off a response.

Specifically, " antigen presenting cells " display their antigens (bits of

a foreign invader) to T-cells, and a resulting physical coupling between

the antigens and the T-cells will prompt the T-cells to divide and

expand in population, triggering an immune response designed to destroy

the invader. This process may take hours.

What the town researchers found, however, is that dendritic cells

-- the most powerful of the antigen-presenting cells and the ones that

can find invaders that have never infected the body and " educate " the

immune system to fight them -- also use serotonin to quickly excite a

T-cell response. They discovered that these dendritic cells can rapidly

secrete serotonin, which activates serotonin receptors on certain types

of T-cells.

" In addition to the physical contact, it surprised us to find that these

immune cells also have machinery to take up serotonin and to secrete it

in an excitatory manner, " Ahern said. " The point behind this

transmission is not entirely clear, but it appears to be an additional

way of stimulating a T cell response. "

Drugs that block serotonin reuptake " likely change some of the

parameters of T-cell activation, but we don't know yet if it enhances or

inhibits the total immune response, " Ahern said. " But it is something

that should be explored because we really have no idea what SSRIs are

doing to people's immune systems. "