RESEARCH LETTER
Effect of Sleep Deprivation
on Response to Immunizaton
To the Editor: Popular wisdom holds that not getting enough
sleep increases the propensity of catching a cold or other ailments. In
America, sleep duration has steadily declined from nearly 9 hours in 1960 to
less than 7 hours currently.1,
2 Although adverse effects of sleep deprivation
on immune parameters have been documented,3
the clinical implications of these findings are unclear. We examined the
effect of sleep deprivation on immune response to influenza vaccination.
Methods
Subjects were 25 healthy young men (mean age, 23 years) who consented to
participate in a protocol approved by our institutional review board.
Eligibility criteria included bedtime between 11 PM and 1 AM, waking time
between 7 and 9 AM, and time in bed of 7.5 to 8.5 hours. None of the
subjects had been immunized against influenza during the preceding 3 years.
Eleven subjects had their bedtime restricted to 4 hours (1-5 AM) for 6
nights and then extended to 12 hours per night for 7 nights to recover from
sleep loss.4 Between
9:00 and 10:00 on the morning following the fourth short night, they were
immunized against influenza (0.5-mL intramuscular injection, Influenza Virus
Vaccine, Trivalent Types A and B, Fluogen, 1996-1997 influenza season,
Parke-Davis, Morris Plains, NJ). A second group of 14 subjects served as
controls and maintained their usual bedtimes prior to receiving the same
vaccine under the same conditions. The 2 groups were recruited from the same
pool of subjects, fulfilled the same inclusion criteria, and did not differ
in terms of age, body mass index, and ethnic background. All subjects were
seropositive for anti-influenza IgG antibody at baseline and mean titers
were similar in both groups.
To assess anti-influenza IgG antibody titers throughout the major phases
of the antibody response, a morning blood sample was taken immediately
before vaccination (baseline), as well as 10 days (during the log phase,
when antibody titer increases logarithmically) and 21 to 30 days (during the
plateau phase, when antibody titer stabilizes) after vaccination. Antibody
titers were measured in all samples using an enzyme-linked immunosorbent
assay, with the vaccine used to immunize the subjects as the antigen.5
Results
Ten days after vaccination, mean (SD) antibody titers in subjects who
were immunized in a state of sleep debt were less than half those measured
in the subjects with normal sleep times (0.50
106 [0.46
106] vs 1.15
106 [1.00
106], respectively;
P = .03 by Mann-Whitney test;
Figure 1). At 3 to 4 weeks after vaccination, antibody titers were no
longer significantly different. Repeated-measures analysis of variance of
natural log-transformed antibody titers with sleep condition as a factor
revealed a significant (P = .04) effect of sleep duration on antibody
titers.
Comment
Sleep deprivation at the time of vaccination reduced the response during
the log phase of antibody production despite a prolonged period of sleep
recovery after vaccination. These results suggest that the response to
influenza vaccination may be impaired in individuals with chronic partial
sleep restriction. Because adults who show poorer responses to vaccines and
other antigenic challenges also experience higher rates of clinical illness,6
our findings support the concept that adequate amounts of sleep are needed
for optimal resistance to infectious challenge.
Karine Spiegel, PhD
Department of Medicine
University of Chicago
Chicago, Ill
John F. Sheridan, PhD
Departments of Oral Biology and Molecular Virology and Immunology
the Ohio State University
Columbus
Eve Van Cauter, PhD
Department of Medicine
University of Chicago
1. Kripke DF, Simons R, Garfinkel L, Hammond E. Short
and long sleep and sleeping pills: is increased mortality associated?
Arch Gen Psychiatry. 1979;36:103-116.
MEDLINE
2. National Sleep Foundation (NSF). 2000 Omnibus
Sleep in America Poll. Washington, DC: NSF; 2000. Available at:
http://www.sleepfoundation.org/publications/2000poll.html. Accessibility
verified August 13, 2002.
3. Krueger JM, Fang J, Floyd RA. Relationship between
sleep and immune function. In: Turek FW, Zee PC, eds. Regulation of Sleep
and Circadian Rhythms. New York, NY: Marcel Dekker Inc; 1999:427-464.
4. Spiegel K, Leproult R, Van Cauter E. Impact of
sleep debt on metabolic and endocrine function. Lancet.
1999;354:1435-1439.
MEDLINE
5. Kiecolt-Glaser JK, Glaser R, Gravenstein S,
Malarkey WB, Sheridan J. Chronic stress alters the immune response to
influenza virus vaccine in older adults. Proc Natl Acad Sci U S A.
1996;93:3043-3047.
MEDLINE
6. McGlone FB, Arden NH. Impact of influenza in
geriatrics and action plan for prevention and treatment. Am J Med.
1987;82(suppl A):55-57.
MEDLINE
Funding/Support: This work was supported by a grant from the
Mind-Body Network of the MacArthur Foundation (Chicago, Ill), and by
National Institutes of Health grants DK-41814 and AG-11412. The General
Clinical Research Center of the University of Chicago is supported by
National Institutes of Health grant M01-RR00055. The vaccine was provided by
Parke-Davis, Morris Plains, NJ.
Acknowledgment: We thank the study participants for their
cooperation and Egidio Colecchia for assistance with data acquisition.
Letters Information
Guidelines for Letters
Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.
