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Commonly used antidepressants may also affect human immune system

January 20, 2006

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 Georgetown 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 Georgetown 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 Georgetown 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."

Georgetown University Medical Center