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Scientists at The Scripps Research Institute Discover Link Between the Immune System and Sleep

La Jolla, CA. January 17, 1996--Scientists at The Scripps Research Institute (TSRI) have discovered a heretofore unknown link between the immune system and sleep cycles, suggesting that the abnormal regulation of certain chemicals released by the immune system may disrupt sleep and lead to disabling fatigue. The discovery may have particular relevance to people with the AIDS virus. Soon after becoming infected most people suffer from severe fatigue that affects their ability to work and lead productive lives.

The study, "Sleep electroencephalogram delta-frequency amplitude, night plasma levels of tumor necrosis factor [alpha], and human immunodeficiency virus infection," appeared in a recent issue of Proceedings of the National Academies of Science.

The scientists studied the cyclical nature of tumor necrosis factor [alpha], peptides from a family known as cytokines that are released by certain cells in the immune system. These cytokines help the immune system to fight off infection.

In HIV patients, however, the cytokines may contribute to symptoms such as incapacitating fatigue long before any other medical problems develop. The researchers found that in both healthy volunteers and in asymptomatic HIV patients, an increase in TNF [alpha] was accompanied by an increase in delta activity -- the slowing of brain activity -- during sleep. This suggests a link between the immune system and sleep cycles and that abnormal regulation of cytokine production may disrupt sleep cycles, leading to disabling fatigue.

The cyclical nature of cytokine production was previously unknown, and occurs in healthy subjects and in asymptomatic individuals with the AIDS virus. With the progression of the disease, however, the association of cytokine level fluctuation and the slowing of brain activity breaks down and becomes uncorrelated.

According to Merrill M. Mitler, Ph.D., member of TSRI's Department of Neuropharmacology and Scientific Director of the Division of Sleep Disorders at Scripps Clinic, "Fatigue is one of the most troublesome aspects of HIV illness. It is high on the list of reasons why patients stop working and stop participating fully as functioning members of society. How to control it is an important question that we must answer if we are to keep AIDS patients engaged and productive."

Currently, tests are underway to evaluate the effects of certain medications that inhibit TNF [alpha] to determine whether this inhibition will help to lessen fatigue, thereby preserving the normal relationship between the production of the peptide and the cyclical nature of brain slowing. According to Mitler, "If TNF [alpha] is causing brain slowing, it also may be causing fatigue. The more we learn about the mechanisms involved, the more we will be able to help patients to lessen this debilitating symptom of AIDS."

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