Sleep and Immune Function

Question:

"How are sleep and immune function connected?"

Vladimir Maletic, MD:
Sleep is just one of the many rhythmic activities that are regulated by the function of our “internal clock.” Hypothalamic suprachiasmatic nucleus (SCN) acts as our personal atomic clock; it is a nexus of pace-making network distributed throughout our brain and body. Secondary timekeepers in the brain include olfactory bulb, amygdala, and hippocampus. Metabolic processes and synthetic activity of liver and even skin cells are synchronized with the activity of SCN. ^1,2 Over millennia of evolution, circadian coordination has become increasingly more complex to include regulation of sleep and wakefulness, hormonal secretion (eg, cortisol and growth hormone), autonomic function, synthesis of neurotransmitters, temperature regulation, motoric activity, and even memory consolidation! ^1,2,3

Melatonin—one of the circadian signaling molecules that helps entrain sleep to external light cycle—also has a prominent role in modulating immune function. ⁴  Conversely, inflammatory cytokines play a major role in sleep initiation. ^5,6  Both are substantially influenced by “stress-modulators”—corticosteroids and norepinephrine. ⁷  Not surprisingly, some conditions characterized by hypothalamic-pituitary-adrenal axis and autonomic disturbance, such as major depressive disorder and chronic pain, tend also to be associated with significant sleep disturbance. ⁸  As a matter of fact, “flattening” of the cortisol curve in patients with depression is correlated not only with severity of depressive symptoms, but also impairment in sleep quality and reduction of total sleep time! ⁹

Recent studies have described elevation of inflammatory cytokines, mediators of innate immunity, during the sleep phase. Conversely, wakefulness is associated by greater activity of acquired immunity manifested by T- and B-lymphocytes and circulating antibodies. Under usual circumstances anti-inflammatory cytokines, such as interleukin-10 (IL-10), have lower levels during sleep and higher levels during the wake hours. Sleep deprivation creates a disturbance in immune regulation: elevation of proinflammatory cytokines (IL-6, IL-12) in the early morning hours with concomitant reduction of anti-inflammatory cytokines (IL-10). ^10-13 This type of immune imbalance commonly leads to a sense of fatigue, sleepiness, body-aches, irritability, anxiety, depressed mood, and diminished concentration ^12,14 ; a state that may conjure up memories of mornings after busy call nights. Elevation of inflammatory cytokines is associated with autonomic disturbance and glucocorticoid receptor insensitivity, often leading to flattening of cortisol curve and functional corticoid insufficiency. ^7,14

No need to spell it out: sleep-immune disturbance is likely to become self-perpetuating. Based on this description, one would expect to find association between sleep and circadian disorders and multiple medical conditions related to increased inflammatory response and immune dysregulation. This is unfortunately true: insomnia and circadian disorders are commonly associated with substantially elevated risk of cardiovascular disease, metabolic syndrome, type II diabetes, obesity, and even cancer. ^15,16  Recent scientific discoveries like the ones connecting somatic illness with sleep-immune disorders have virtually rendered Cartesian mind-body duality obsolete.

–Vladimir Maletic, MD

References

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