Systems biology of circadian-immune interactions

P. D. Mavroudis, J. D. Scheff, S. E. Calvano, I. P. Androulakis

Research output: Contribution to journalReview articlepeer-review

45 Scopus citations


There is increasing evidence that the immune system is regulated by circadian rhythms. A wide range of immune parameters, such as the number of red blood cells and peripheral blood mononuclear cells as well as the level of critical immune mediators, such as cytokines, undergo daily fluctuations. Current experimental data indicate that circadian information reaches immune tissues mainly through diurnal patterns of autonomic and endocrine rhythms. In addition, immune factors such as cytokines can also influence the phase of the circadian clock, providing bidirectional flow of circadian information between the neuroendocrine and immune systems. This network of neuroendocrine-immune interactions consists of complexly integrated molecular feedback and feedforward loops that function in synchrony in order to optimize immune response. Chronic stress can disrupt this intrinsic orchestration, as several endocrine signals of chronically stressed patients present blunted rhythmic characteristics. Reprogramming of biological rhythms has recently gained much attention as a potent method to leverage homeostatic circadian controls to ultimately improve clinical outcomes. Elucidation of the intrinsic properties of such complex systems and optimization of intervention strategies require not only an accurate identification of the signaling pathways that mediate host responses, but also a system-level description and evaluation.

Original languageEnglish (US)
Pages (from-to)153-162
Number of pages10
JournalJournal of Innate Immunity
Issue number2
StatePublished - Mar 2013

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy


  • Circadian reprogramming
  • Circadian rhythm
  • Clock entrainment
  • Clock genes
  • Clock synchronization
  • Immune response
  • Inflammatory response


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