Corresponding author e-mail: dgolombek@unq.edu.ar Circadian rhythms are ubiquitous in nature, and control temporal order in most (if not all) physiological systems. Indeed, most immune factors and processes are under diurnal control, orchestrated by the circadian system, although the efferent pathways that control these cycles are not completely understood. In addition, circadian disorders are usually associated with disease, and temporal disarrangements in immune parameters are closely related to the onset or development of pathological mechanisms. In the last few years we have been working under the hypothesis that the circadian-immune interaction can operate in two directions. First, daily cycles in immune parameters are controlled by the central circadian pacemaker located at the hypothalamic SCN. On the other hand, these same temporal variations might be useful for a fine-tuning of the system by affecting receptors located in the circadian clock. We have provided evidence suggesting that this latter interaction might be mediated by glial cells that respond to peripheral or central cytokines which by different transcriptional activators affect molecular circadian rhythms. In particular, we have shown that an endotoxin (LPS) challenge is able to set the phase of locomotor activity circadian rhythms, reaching the SCN through a Toll-4 receptor activation and proinflammatory cytokine signal transduction pathways. Cytokines are also able to affect entrainment and SCN gene expression in vivo and clock gene expression in vitro. We have previously demonstrated that NFkB-related transcription is also involved in entrainment, opening a new window into the regulation of gene expression in relation to circadian rhythmicity. Indeed, the precise knowledge of this circadian-immune interaction might be extremely useful for the understanding of why many infections and illnesses affect circadian rhythms (including the sleep-wake cycle) and greatly decrease the patients’ quality of life. Besides a better understanding of the physiological regulation of circadian rhythmicity, the chronobiological basis of the times to kill and the times to heal will therefore provide a novel basis for diagnosis and therapeutical approaches in order to treat disease. When the circadian orchestra is out of tune or rhythm, a precise knowledge of immune-circadian interactions might be helpful for regaining the musical control of the body. Publication History Article published online: 16 June 2026 © 2009. Brazilian Sleep Academy. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/) Thieme Revinter Publicações Ltda. Rua Rego Freitas, 175, loja 1, República, São Paulo, SP, CEP 01220-010, Brazil
DA Golombek (2009) studied this question.