Serotonin, Melatonin, Immunity and Cancer

Making connections (from January 22, 2006)...

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I love Miss Frizzle from the cartoon "The Magic School Bus". She always says "Make connections, kids, make connections!" Here I'll try to make some tentative connections between two recent papers, both concerning health issues in humans.

The first paper, brought to my attention by Corpus Callosum, a blog I belatedly placed on my blogroll here only today, is titled Commonly Used Antidepressants May Also Affect Human Immune System, which is a high-hype way of presenting a finding that some types of immune cells appear to communicate using serotonin as a signal. To be precise, the dendritic cells, a type of antigen-presenting cell in the immune system, can uptake and relase serotonin, which in turn excites T-cells in a rapid fashion. Thus, manipulation of serotonin by pharmacological agents (as in treatment of depression) may have - as yet unknown - effects on the immune system.

Well, I have a hammer so I see nails everywhere. Whenever I see "serotonin" I wonder if melatonin is also involved. Why? Because the two appear to be connected almost in everything.

First, serotonin is a biochemical precursor of melatonin (you can see the pathway here). Thus, if there is more serotonin now, there can potentially be more melatonin later. If serotonin is lacking now, there will be a lack of melatonin later.

Second, the two substances appear to be ubiquitous throughut the body and their receptors are found apparently everywhere (what are Melatonin receptors doing in the quail ovaries and eggs?).

Third, the two substances almost always have opposite effects. While one stimulates intestinal movement, the other one inhibits it. There are many examples of such antagonism.

And, it has been known for a while now that melatonin enhances immune response. My friend and colleague Chris Moore published several papers on this topic. For instance, in this paper, he showed that exposure to constant light, which supresses melatonin synthesis and release, inhibits both the cellular and the humoral immunity, and that addition of melatonin to drinking water boosts immunity in a dose-dependent manner in quail kept in constant light. In another paper he showed that supression of melatonin by light is not neccessary for additional melatonin to boost the immune response beyond that seen normally. Also, it appears that melatonin enhances immunity via an opiate route. Finally, removing one source of melatonin, the pineal, reduced the immune response, while, strangely, removal of the other source of melatonin, the eyes, did not have an effect.

So, if melatonin boosts immunity, we can expect serotonin to do the opposite, i.e., to supress the immune response. Does that mean that taking Prozac is bad for your immune response? Who knows - it is too early to tell.

The second paper comes by the way of Tara Smith from Aetiology, one of the dozen or so science bloggers who recently joined the Seed group's ScienceBlogs (also added to my blogroll today). She explains it very well in her post, so head over there for more.

In the paper, a series of experiments in nude rats with hepatomas and in rats with transplants of human breast cancer tissue, shows that a) exposure to constant light decreases melatonin, b) both the rat and the human cancer cells express melatonin receptors, c) perfusion with melatonin-rich blood slows down cancer and d) perfusion with melatonin-depleted blood speeds up cancer. Out of several different treatments, one of the types of melatonin-depleted blood came from women working in bright light during night shift.

The effect of melatonin on cancer tissues was direct, via a linoleic acid pathway. But, considering the paper I discussed above, isn't it reasonable to expect that effects of bright light at night will also have an effect on immunity, i.e., the supression of melatonin release would supress immune response and also allow the cancers to form and spread? It is well known, after all, thet night-shift nurses tend to suffer much more, from a variety of diseases including breats cancer, than nurses that always work day-shifts.

Finally, melatonin does not work only directly, as a hormone. It is also a signal of time. A person working on a rotating shift is constantly 'jet-lagged', i.e., all the little clocks in various tissues are out of sync with each other. This in itself, melatonin or no melatonin, should be pretty bad for one's health. After all, in a spectacular series of experiments in 1950s, Dr.Janet Harker showed that cockroaches containing two pacemakers entrained several hours out of phase with each other (e.g., NYC time in the left lobe and New Zealand time in the right lobe) developed intestinal cancer - something rarely seen in insects.