Circadian Rhythm and the Immune Response: A Review

Abstract

For long, the immune system has been thought of as an effector mechanism reacting to antigenic challenge with defensive responses designed to eliminate 'foreign' material and return to a standby or surveillance mode. However, the recent concept now supported by substantial evidence suggests that immunity is not effector biased but is also a sensory organ and forms part of an integrated homeostatic network. The bidirectional information flow between the neuroendocrine and immune systems functions to maintain and protect the internal homeostasis of the organism. The paradox of this interwined function is that homeostasis may require the neuroendocrine system to work for or against the immune system, as is the case in infection. Potential dangers necessitate activation of the immune system, and such a response may pose risks to the integrity of the host. This occurs when an overly vigorous response may be detrimental and kill the host, as is the case of toxic shock syndrome. Therefore, the constant monitoring role of the neuroendocrine system to control and, when necessary, regulate the function of the immune system is crucial for the homeostatic integrity of the host. This reciprocity of functional need determines the mode of action to determine the context of a perceived threat and the best way to respond. Any breakdown in this two-way communication may manifest itself in problems such as autoimmunity, septic shock, or chronic infection. In this article, we review our current knowledge of circadian rhythm and its relation to the immune response.

Sex-Related Differences in Gene Expression Following Coxiella burnetii Infection in Mice: Potential Role of Circadian Rhythm

“…Orchidectomy leads to a loss of androgen receptor expression and circadian-specific locomotor activity, both of which are restored by testosterone replacement [49], [50]. Interestingly, circadian rhythm and immune responses are interconnected [51]. For instance, the susceptibility or resistance of flies to infection varies according to the time when they are infected [52].…”

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“…Furthermore, delirious patients experience a loss of day-night orientation, have significant disruption to regular sleep patterns and are frequently sleep deprived [15]. A number of immunological functions are dependent on circadian rhythms and regular sleep, and those who are sleep deprived are therefore less able to mount an appropriate immune response to pathogens [16]. …”

Pronounced Inflammatory Response to Endotoxaemia during Nighttime: A Randomised Cross-Over Trial

“…The existence of circadian variation in acute medical settings is well established [1]–[3]. The occurrence of acute myocardial infarction, sudden cardiac death, pulmonary thromboembolisms and stroke exhibits a distinct circadian variation [4].…”