Are Cytokines Causing Your sleep problems

[Guest guest]

Interesting article.GOt off the The amerian Fibromyalgia Syndrome

Asociation web page. Heidi

Are Cytokines Causing Your Sleep Problems?

Natelson, M.D., is nearing the end of his four-year National

Institutes of Health (NIH) project on the role of sleep disturbances,

exercise, and cytokine production in chronic fatigue syndrome (CFS)

and fibromyalgia syndrome (FMS) patients. At the beginning of 2006,

AFSA funded a tag-on study to this NIH grant to evaluate two

additional cytokines that are known to be elevated in FMS patients:

interleukin-6 (IL-6) and interleukin-8 (IL-8). Cytokines are

substances secreted by immune cells throughout the body, including

the central nervous system where the glial cells reside. The box

below indicates how IL-6 and IL-8, in addition to the many other

cytokines that Natelson is measuring, might be involved in the

symptoms of pain, fatigue, and disturbed sleep.

All cytokine studies to date involving CFS or FMS patients have only

looked at the level of these substances in the blood at one time

during the day (i.e., just a single blood sample). While this

approach is a good place to start, it does not reveal whether

specific cytokines might be contributing to disturbed sleep. Natelson

collected blood samples at bedtime, three times during the night, and

then upon awakening. He did this for three nights (not necessarily in

a row) while the participants (patients and healthy controls) were

put through various daytime tests, including an exercise protocol.

Natelson's project design represents a giant leap forward to detect

an altered rhythm of cytokine production that may be associated with

disturbed sleep, daytime fatigue, and pain.

Natelson's entire NIH study—including the small portion funded by

AFSA—provides an innovative way to look at sleep and the many

complexities of CFS and FMS. He answers several questions about his

project to keep contributors to AFSA informed about his progress.

Actions of Cytokines

IL-6: causes fatigue, pain, and cognitive dysfunction

IL-8: causes pain

IL-1, TNF: sleep enhancers/pain promoters

IL-4, IL-10: sleep disruptors/pain relievers

Q & A with Dr. Natelson

How far along are you on this project?

Our sleep studies are done and we've just finished doing all our

cytokine assays. A postdoctoral fellow just joined our research team,

and his primary task will be to look at the various interactions or

associations among the data. This part will take some time because of

the tremendous amount of information and the complexity of the data

we've collected.

Your hypothesis is that cytokines disrupt sleep and not the other way

around. What do you suspect might be causing the alterations in

cytokine production?

That's the 64 million dollar question. There are so many possible

answers that have not yet been explored, and any response I provide

would just be speculation at this point. Perhaps a virus or the

existence of a brain malfunction induces an alteration of the immune

system, causing changes in cytokine production and producing chronic

sleep disruption. These are just possibilities.

AFSA's role was to fund the analysis of two additional cytokines (IL-

6 and IL-8). Could you explain the importance of this part of your

project?

I particularly wanted to add IL-8 because there are data in the

scientific literature showing that this cytokine is affected in FMS.

IL-6 is the most common cytokine studied in a number of disorders

involving physiological challenge conditions. For example, it is

elevated in people with impaired sleep quality. Of interest is a

recent paper reporting elevations in both IL-6 and IL-8 in patients

with irritable bowel syndrome.

When do you expect the cytokine results to be published, and do you

anticipate that it might generate several different papers?

With partial support from AFSA, we did look at cytokines in FMS

patients over the 24-hour time period. Our goal in doing these

studies was to look across time at a number of cytokines to determine

if these differed in FMS compared to healthy controls. Those data

have been extremely complex, but after a year's worth of work we are

just about done with the analyses. We are in the process of writing

up the study, and this will represent the first sleep and cytokine

data to come out of my lab. As for the rest of our study data, I am

confident that they will generate several more research papers.

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