Cavadini, Gionata Petrzilka, Saskia Kohler, Philipp Jud, Corinne Tobler, Irene 2007-06-23 Production of TNF-α and IL-1 in infectious and autoimmune diseases is associated with fever, fatigue, and sleep disturbances, which are collectively referred to as sickness behavior syndrome. In mice TNF-α and IL-1 increase nonrapid eye movement sleep. Because clock genes regulate the circadian rhythm and thereby locomotor activity and may alter sleep architecture we assessed the influence of TNF-α on the circadian timing system. TNF-α is shown here to suppress the expression of the PAR bZip clock-controlled genes <i>Dbp</i>, <i>Tef</i>, and <i>Hlf</i> and of the period genes <i>Per1</i>, <i>Per2</i>, and <i>Per3</i> in fibroblasts <i>in vitro</i> and <i>in vivo</i> in the liver of mice infused with the cytokine. The effect of TNF-α on clock genes is shared by IL-1β, but not by IFN-α, and IL-6. Furthermore, TNF-α interferes with the expression of <i>Dbp</i> in the suprachiasmatic nucleus and causes prolonged rest periods in the dark when mice show spontaneous locomotor activity. Using clock reporter genes TNF-α is found here to inhibit CLOCK-BMAL1-induced activation of E-box regulatory elements-dependent clock gene promoters. We suggest that the increase of TNF-α and IL-1β, as seen in infectious and autoimmune diseases, impairs clock gene functions and causes fatigue. application/pdf https://folia.unifr.ch/global/documents/300468 https://folia.unifr.ch/documents/300468/files/jud_tse.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.0701466104 info:eu-repo/semantics/openAccess License undefined Proceedings of the National Academy of Sciences of the United States of America. - 2007, vol. 104, no. 31, p. 12843-12848 behavior circadian rhythms cytokines innate immunity info:eu-repo/classification/udc/57 TNF-α suppresses the expression of clock genes by interfering with E-box-mediated transcription http://purl.org/coar/resource_type/c_6501