Introduction Evidence Is Mounting That Sleep Is Not Merely a Passive State of Relaxation to Compensate for Fatigue Accumulated during Waking

EVIDENCE IS MOUNTING THAT SLEEP IS NOT MERELY A PASSIVE STATE OF RELAXATION TO COMPENSATE FOR FATIGUE ACCUMULATED DURING WAKING HOURS. For example, reports indicate that it plays a role in active modification of host defense functions.1 To evaluate the effects of natural sleep on neuroendocrine immune function, numerous research groups have investigated changes in certain immune functions when healthy subjects were subjected to total or partial sleep deprivation. Several of these groups have focused their attention on the effect of sleep deprivation on natural killer (NK) cell activity. NK cells are lymphocytes that lack antigenic specificity and are found in normal individuals. They are believed to play a role in mediating natural resistance against tumors and infections. Research to date has produced divergent findings on the effect of total or partial sleep deprivation on NK cell number and/or activity.2-6 Dinges et al. have investigated the effect of 64-hour sustained awake on NK cell activity in 20 young adults, and reported that NK cell activity increased during total sleep deprivation which effect were eliminated by recovery sleep.3 Born et al. have also found that NK cell numbers transiently increased during total sleep deprivation in 10 young male volunteers although they decreased until the following afternoon.2 Contrary to these findings, Moldofsky and his colleagues have indicated that total sleep deprivation could reduce NK cell activity in healthy male volunteers, as was also suggested by studies by Irwin et al. in which late-night partial sleep deprivation was applied.5,6 There are several possible causes for the differences in the research findings concerning the effect of sleep deprivation on immune function. The first potential cause is the effect of circadian variation on immune function. It has been reported that clear-cut daily variations are present at several levels of cellular immune function, including NK cell count, NK cell activity, CD4 and CD8 cell count, and the lymphoblast response to factors such as PHA and Con-A.2,7-10 Because the circadian rhythm phase is determined by interactions between the suprachiasmatic nucleus (in which the biological clock is located) and the external environment (including the light environment), there is considerable inter-individual variation that is dependent on the subject’s sleep/waking phase immediately before entering the study. When evaluating changes in cellular immune function induced by sleep deprivation, it is therefore essential to adopt a cross-over design composed of natural sleep and sleep deprivation conditions as well as to collect blood samples at the same circadian rhythm phase between both conditions, rather than at the same clock time. The second potential cause is the effect of the increase in physical exercise—an inevitable result of sleep deprivation in the absence of specific controls—on immune function. A meta-analysis of several research projects has demonstrated that an increase in physical exercise typically produces a significant short-term change in peripheral NK cell count or NK cell activity.11 However, to our knowledge, we are unaware of any research in which circadian rhythm and physical exercise during sleep deprivation were adequately analyzed and controlled for each subject. In the present work, we investigated the effect of sleep deprivation on NK cell activity in peripheral blood in healthy young adult subjects, rigorously controlling the amount of exercise, posture, and circadian rhythm phase, in a cross-over study design