Shift of monocyte function toward cellular immunity during sleep.
BACKGROUND
Sleep is considered to strengthen immune defense. We hypothesized that sleep achieves this effect by shifting the balance between types 1 and 2 cytokine activity toward increased type 1 activity, thereby supporting adaptive cellular immune responses.


METHODS
We analyzed monocyte-derived type 1 (interleukin 12 [IL-12]) and type 2 (IL-10) cytokines by means of multiparametric flow cytometry in healthy human subjects (n = 11) during a regular sleep-wake cycle and 24 hours of wakefulness.


RESULTS
Sleep increased the number of IL-12-producing monocytes and concurrently decreased the number of IL-10-producing monocytes, thereby inducing clear rhythms in these cells, with maximum numbers at 2:20 and 11:30 am, respectively. The rhythms were completely absent during continuous wakefulness. Correlation analyses and supplementary in vitro studies suggest that high prolactin and low cortisol levels are factors contributing to the shift in the IL-12/IL-10 ratio toward increased IL-12 activity during sleep.


CONCLUSIONS
Monocyte-derived IL-12 and IL-10 play a critical role for tuning the synapse between antigen-presenting cells and lymphocytes. By preferentially supporting type 1 IL-12 activity, sleep induces a 24-hour oscillation between predominant types 1 and 2 cytokines and, in this way, acts to globally increase the efficacy of adaptive immune responses. Improving sleep could represent a therapeutic option to enhance the success of vaccinations and success in the treatment of diseases (eg, atopic dermatitis and human immunodeficiency virus infection) that are characterized by type 2 cytokine overactivity.
Lange
Tanja
T
Department of Internal Medicine, University of Lübeck, Lübeck, Germany.
Dimitrov
Stoyan
S
Fehm
Horst-Lorenz
HL
Westermann
Jürgen
J
Born
Jan
J
D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology; D018592:Cross-Over Studies; D005434:Flow Cytometry; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D017286:Polysomnography; D011388:Prolactin / Q000097:blood; D012890:Sleep / Q000276:immunology* / Q000502:physiology; D014851:Wakefulness / Q000502:physiology
D016753:Interleukin-10; D018664:Interleukin-12; D011388:Prolactin; D013006:Growth Hormone; D006854:Hydrocortisone; D009638:Norepinephrine