The general pattern in both animals and humans is that sleep is increased during infection (Toth and Krueger 1988). In general, animals appear to show an increase in stage 3 and 4 slow-wave sleep (SWS) of nonrapid eye movement (NREM) and decreased rapid eye movement (REM) sleep (Bryant, Trinder, and Curtis 2004). Infection with influenza virus in human causes reduced sleep during the incubation period but increased sleep during the symptomatic period (Smith 1992). Exposure to microbial components such as lipopolysaccaride and muramyl peptides mimics the sleep effect (Mullington et al. 2000). Finally, increases in the intracerebral or plasma levels of TNF or IL1-P result in an increase in SWS duration, whereas antagonizing these cytokines with specific antibodies inhibit SWS (Opp and Krueger 1994). It appears that most proinflammatory cytokines are somnogenic, whereas most anti-inflammatory cytokines are not.
Neuroendocrine hormones produced by the hypothalamus influence sleep. Thus, CRH is a potent inducer of waking while GHRH promotes SWS (Obal, Fang, Payne, and Krueger 1995; Opp and Imeri 2001). These same hormones are produced by cells of the immune system (Weigent and Blalock 1995) and thus the immune and nervous system share regulatory molecules which supports their ability to interact. There are some data to suggest that chronic sleep loss might be detrimental to the immune system. Thus, sleep deprivation in nonimmune mice appeared to impede the clearance of influenza virus along the respiratory tract (Renegar, Crouse, Floyd, and Krueger 2000).
Also, sleep-deprived humans immunized against infection with influenza virus had lower virus-specific antibody titers compared to non-sleep-deprived individuals (Spiegel, Sheridan, and Van Cauter 2002). Despite the evidence that sleep loss has effects on immune function and secretion of cytokines, the significance of these changes on the immune response is not known (Irwin 2002). Finally, illnesses such as chronic fatigue, fibromyalgia and depression show NREM sleep disruption (Moldofsky 1993). Primary sleep disorders are also associated with alterations in immune competence (Sakami et al. 2002). Thus, decreases in the numbers of CD3+, CD4+, and CD8+ T cells and reduced NK cell responses have been associated with chronic insomnia (Savard, Laroche, Simard, Ivers, and Morin 2003).
There is a strong association of HLA molecules and impaired transmission of hypocretin with narcolepsy (Lin, Hungs, and Mignot 2001). IFN-a has been shown to inhibit the production of hypocretin, supporting the hypothesis of a connection between sleep and the immune system. Taken together, the growing amount of data show that there is a reciprocal relationship or bidirectional communication between sleep and immunity.
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