Sunday, January 22, 2006

Immune System and Serotonin

There is a complex relationship between the immune system and the human brain.  A discussion of that is way beyond the scope of a simple blog post, but I trust anyone reading this knows how to look into the subject if interested.  (Hint: Google immune system brain and you get over nine million hits.)  Now comes a study that shows that the relationship between the brain and the immune system is more complex than previously recognized.  Certain immune system cells communicate using serotonin, which is one of the major chemical messengers in the brain.  That means that factors that affect signals in the brain also can affect signals between immune system cells.
Commonly Used Antidepressants May Also Affect Human Immune System

Washington, D.C. -- 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. [...]
The article goes on to say that the researchers do not know if antidepressants increase or decrease (or alter in some other way) the action of the immune system cells that they were studying.  In fact, they don't know if they have any effect at all.  The real significance of the study is not that antidepressants might affect the immune system; rather, it is that some immune system cells communicate with each other in a way that was not recognized previously.  The implication is that it might be difficult for us to perform interventions on the brain without also affecting the immune system.  

A few points of clarification are in order.  The immune system cells that were found to use serotonin to communicate are called dendritic cells.  This has nothing to do with the parts of nerve cells called dendrites.  Also, note that some non-SSRI antidepressants, such as the tricyclic antidepressants, affect serotonin in the same way that SSRIs do.  The specific reference to SSRIs is probably a journalistic tactic to get the attention of readers, sort of like making an offhand reference to Paris Hilton, when the story really is not about Paris Hilton.

Another thing to keep in mind about the study, is that when nerve cells communicate using serotonin, those cells are in a fixed position, right next to each other.  The reuptake of serotonin is one of the three ways that the signal from the serotonin is turned off.  In the case of immune cell communication, the cells are not fixed in close proximity, thus passive diffusion of the serotonin is probably much more important than the reuptake mechanism.  Furthermore, when nerve cells communicate, the precise timing, duration, and frequency of the stimulation are all very important factors.  Thus, anything that modulates the signal has the potential to be very important.  In contrast, it appears that the exact character of the signal (timing, duration, frequency) between immune cells is not so critical.  Therefore, it may not matter very much if a drug inhibits the reuptake of serotonin into a dendritic cell.  

On the other hand, it might matter a great deal.  That is one of the points made by the Dr. Ahem:
“But it is something that should be explored because we really have no idea what SSRIs are doing to people’s immune systems.”
At first, that statement may seem alarming.  But in fact, you could write any statement about a class of chemicals Xs and a physiological system Y, in the form...

We really have no idea what Xs are doing to people's Y systems

...and it probably would be true.  So while we cannot really ignore it, at this point I would not make much of it, either.  What is important about the study is that is shows yet again how complex these systems are, and how little we know about them.  Although it does not give us a specific reason to worry, it does illustrate why, in general, we should be circumspect about putting chemicals into people's bodies.