Immune System Affects Circadian Clock During Illness

Inflammatory cytokines shut down genes controlling circadian rhythm

WEDNESDAY, July 25 (HealthDay News) -- Sleepiness that commonly occurs during illness or infection may be caused by inhibition of circadian rhythm genes by the inflammatory cytokine TNF-α, according to the results of a study in cultured cells and in mice published online July 23 in the Proceedings of the National Academy of Sciences Early Edition.

Thomas Birchler, Ph.D., from the University of Zurich in Switzerland, and colleagues assessed the influence of TNF-α on the circadian rhythm timing system in both cells and in mice.

The investigators found that TNF-α and IL-1β, but not other cytokines, suppressed expression of several genes in fibroblasts that are known to control circadian rhythms including Dbp, Tef, Hlf and the period genes. TNF-α was shown to inhibit these genes through interference with an E-box regulatory element. Mice treated with TNF-α showed reduced expression of Dbp in the suprachiasmatic nucleus and prolonged rest periods.

"The 'inflammatory clock gene response' may, by inducing fatigue, diminish the quality of life in autoimmune diseases," the authors write. "Our study will serve to lay an important foundation for further exploration of the connection between the TNF-α-induced 'inflammatory clock gene response' and the TNF-α-triggered reduction of locomotor activity."

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