Body Clock Shift May Cause Sickness-Linked Fatigue

Targeting this change could lead to new therapies, researchers say.

By E.J. Mundell
HealthDay Reporter
Thursday, July 19, 2007; 12:00 AM

Copyright © 2007 ScoutNews, LLC. All rights reserved.

THURSDAY, July 19 (HealthDay News) -- As anyone who has battled the flu knows, "sick and tired" often go hand-in-hand.

Now, research suggests that illness-linked biochemistry may interfere with the body's "clock" to bring on the low-energy blahs.

Especially for patients battling chronic fatigue, the new findings "could pave the way for further exploration of the interaction between the immune system and the circadian system, hopefully leading to a better understanding of how daytime fatigue could be treated," said study co-lead researcher Thomas Birchler, of the University Hospital Zurich, in Switzerland.

His team published its findings in this week's online edition of the Proceedings of the National Academy of Sciences.

A sudden, profound loss of daytime energy is one of those "uh-oh" symptoms that signals the onset of acute illness, such as colds or influenza. Fatigue of a more chronic kind is also one of the most common and debilitating hallmarks of a wide variety of disorders, from cancer to autoimmune disease to Chronic Fatigue Syndrome.

Up until now, however, scientists knew little as to why fatigue so often accompanies illness.

In the new study, Birchler's team sought to determine how TNF-alpha -- an immune system inflammatory protein or "cytokine" -- might induce daytime tiredness.

A jump in TNF-alpha activity "is found in most of the acute and chronic infectious diseases and is also part of the inflammatory response in autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and Crohn's disease," Birchler explained.

TNF-alpha helps spur immune-fighting cells that then seek out and destroy the agent causing the illness.

However, the Swiss group's work with both cell cultures and mice found that TNF-alpha has other physiological effects.

"Besides the known functions of TNF-alpha to eliminate infectious agents, we provide evidence that TNF-alpha interferes with clock gene expression," Birchler said.

In other words, the cytokine may affect genes that, in turn, upset the body's normal sleep/wake rhythms -- the "biological clock." This circadian clock guides the daily cycle of alertness and fatigue that people typically feel when healthy, but TNF-alpha appears to help put this cycle into disarray.