Depression and severity of depressive symptoms have been associated with alterations of cell-mediated immune function. Sleep disturbance might play a role in the reduction of NK activity since severity of insomnia has been found to be a distinct correlate of reduced NK activity in depressed patients separate from the contribution of other depressive symptoms. Furthermore, a reduction of NK activity has also been found in persons undergoing marked adversity who report insomnia but no other symptoms of depression. Despite these clinical data that suggest a distinct association between reduced natural cytotoxicity and insomnia, no study has yet tested whether objective assessments of sleepwake activity might be associated with alterations in immune function, even though it is well recognized that objective sleep EEG measurement is a more reliable assessment of sleep than self reports of insomnia. Our recent preliminary work involving measurement.of EEG sleep suggests that disturbances of sleep continuity, sleep architecture, and REM sleep are indeed correlated with reduced cytotoxicity. In addition, plasma levels of IL-2 have been found to mediate the association between depressive symptoms and NK activity in depressed patients. Finally, consistent with previous findings, nocturnal secretion of IL-2 has been found to occur in sleeping subjects. This research will be extended by the following aims: 1) to establish further the relationship between-sleep-wake activity and natural killer cytotoxicity; 2) to characterize the role of sleep activity in the secretion of lymphokines; 3) to examine whether the nocturnal secretion of IL-1 and IL-2 mediates the association between sleep disturbance and altered NK activity. In summary, the findings of this study have the potential to demonstrate that sleep-wake activity has a role in mediating cellular immunity, further implicating nocturnal secretion of immune response modifiers as an underlying mechanism that links sleep alterations and disturbed immune function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH046867-03
Application #
2247290
Study Section
Clinical Neuroscience Review Committee (CNR)
Project Start
1992-09-01
Project End
1995-12-31
Budget Start
1994-09-01
Budget End
1995-12-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Irwin, M; Hauger, R; Patterson, T L et al. (1997) Alzheimer caregiver stress: basal natural killer cell activity, pituitary-adrenal cortical function, and sympathetic tone. Ann Behav Med 19:83-90
Pike, J L; Smith, T L; Hauger, R L et al. (1997) Chronic life stress alters sympathetic, neuroendocrine, and immune responsivity to an acute psychological stressor in humans. Psychosom Med 59:447-57
Irwin, M; McClintick, J; Costlow, C et al. (1996) Partial night sleep deprivation reduces natural killer and cellular immune responses in humans. FASEB J 10:643-53
Friedman, E M; Irwin, M R (1995) A role for CRH and the sympathetic nervous system in stress-induced immunosuppression. Ann N Y Acad Sci 771:396-418
Zisook, S; Shuchter, S R; Irwin, M et al. (1994) Bereavement, depression, and immune function. Psychiatry Res 52:1-10
Cover, H; Irwin, M (1994) Immunity and depression: insomnia, retardation, and reduction of natural killer cell activity. J Behav Med 17:217-23
Irwin, M (1994) Stress-induced immune suppression: role of brain corticotropin releasing hormone and autonomic nervous system mechanisms. Adv Neuroimmunol 4:29-47
Irwin, M; Mascovich, A; Gillin, J C et al. (1994) Partial sleep deprivation reduces natural killer cell activity in humans. Psychosom Med 56:493-8
Irwin, M (1993) Brain corticotropin-releasing hormone- and interleukin-1 beta-induced suppression of specific antibody production. Endocrinology 133:1352-60
Irwin, M (1993) Stress-induced immune suppression. Role of the autonomic nervous system. Ann N Y Acad Sci 697:203-18

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