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Circadian variation occurs in immunocompetent cells and cytokines as an anticipatory process for the preservation of body homeostasis and defence (Cermakian et al., 2013). Cytokines are small protein cells responsible for cell signalling. The IS shows reliable daily variations, for example immunocompetent cell counts and cytokine levels vary according to the time of day and the sleep–wake cycle. Different immune cell types, such as macrophages, natural killer (or NK) cells, and lymphocytes, all contain circadian molecular clockwork.

The biological clocks of immune cells and lymphoid organs, together with the central pacemaker of the suprachiasmatic nuclei via humoural and neural pathways, regulate the IS, including its response to signals and their effector functions. There is a diurnal variation in the response to immune challenges (e.g., a bacterial injection) and circadian control of allergic reactions. The circadian–immune connection is bidirectional, and immune challenges and immune mediators (e.g., cytokines) affect circadian rhythms at the molecular, cellular and behavioural levels. Cross-talk between the circadian and immune systems has implications for disease, as shown by the higher incidence of cancer and the exacerbation of autoimmune symptoms upon circadian disruption (Cermakian et al., 2013).