University of Toronto Centre for Sleep and Chronobiology
The Toronto Hospital, Western Division
Toronto, Canada MST 2S8
ecent animal and human studies show that the immune-neuroendocrine-thermal operations of the body are intimately linked to the sleeping-waking brain. In humans, the diurnal pattern of aspects of cellular immune functions in the peripheral circulation is related to the sleep-wake cycle, e.g., mitogen stimulation response, proportion and cytotoxicity of natural killer (NK) cells, and proportion of T cells. Such cytokines as interleukin-l(IL-1), IL-6 and gamma INF are also linked to human sleep. These cellular and cytokine functions are related to diurnal changes in growth hormone (GH), prolactin, and cortisol secretion.
Sleep deprivation results in increased IL-1 activities, decreased GH secretion and an alteration in mitogen responses and NK cytotoxicity during nocturnal wakefulness. There are gender differences in sleep-related cellular immune functions. During the low progesterone phase of the menstrual cycle, the sleep/wake-related changes in PHA mitogen responses and NK cell activities in young women are similar to those occurring in young men. However, in the high progesterone phase there is a delay in the onset to and a reduction in slow wave sleep (SWS) that are accompanied by a delay in the sleep-related decline in NK cytotoxicity.
Sleep, immune and endocrine functions are altered by illness. Host response to acute infection with endotoxin challenge results in increased NREM but disrupted sleep and increased TNFa, IL-6, ILra and cortisol, but a subpyrogenic low dose endotoxin results in increased SWS. Patients with trypanosomiasis show disruption in the temporal organization of sleep/wakefulness, neuroendocrine and cytokine functions. Preliminary data indicate an alteration in the circadian pattern of NK cell functions in chronic fatigue syndrome/fibromyalgia.
The research is consistent with the theory that the harmonious interrelationship of the circadian patterns of the immune, neuroendocrine, thermal and brain activities are important for the cause and functions of sleep. Infection promotes sleep and alters these immune-endocrine-thermal regulatory responses. Disturbance of the sleep/wake system is accompanied by dysregulation of these functions of the body and may contribute to chronic fatigue illnesses such as fibromyalgia and chronic fatigue syndrome.
