Sleep and Immune Function: Cytokines, NK Cells, and Vaccine Response
One night of sleep deprivation reduces NK cell activity by 28%; sleeping <6h reduces hepatitis B vaccine antibody response 11.5× compared to 7+ hour sleepers; IL-6 and TNF-α peak during NREM sleep.
| Measure | Value | Unit | Notes |
|---|---|---|---|
| NK cell reduction after one night deprivation | 28 | % reduction | Irwin et al. 1994; partial night (0–3am awake) was sufficient for this effect |
| Vaccine antibody at <6h sleep | 11.5× | lower antibody titer | Hepatitis B vaccine; Spiegel et al. 2002; 7+ hour sleepers had much better response |
| Cold susceptibility at <7h sleep | 3× | increased risk | Prather et al. 2015; rhinovirus challenge study (n=164); dose-response relationship |
| IL-6 peak | NREM sleep | sleep stage | Interleukin-6 and TNF-alpha secreted preferentially during slow-wave sleep |
| T-cell trafficking | +Naive T cells to lymph nodes | migration | Nocturnal immune cell redistribution to lymph nodes during NREM (Born 1997) |
Sleep as an Active Immune State
Contrary to the intuitive view of sleep as metabolic rest, the immune system is highly active during sleep. NREM sleep in particular coordinates several immune processes:
- Cytokine release: IL-1β, TNF-α, and IL-6 — the primary pro-inflammatory cytokines — are secreted preferentially during NREM sleep. This is partially circadian but also directly linked to sleep itself.
- T-cell redistribution: Born et al. (1997) demonstrated that naive T cells and natural killer cells redistribute from blood to lymph nodes during early night NREM sleep, returning to circulation in the morning. This nocturnal trafficking optimizes immune surveillance.
- Growth hormone as immune modulator: the GH surge during SWS stimulates immune effector cells and lymphoid tissue growth
The bidirectional relationship between sleep and immunity is fundamental: immune activation (infection, vaccination, injury) increases sleep duration and SWS depth, and sleep deprivation impairs immune function — a reciprocal regulatory loop that evolved to coordinate host defense with physiological restoration.
Vaccine Response
One of the most striking demonstrations of sleep’s immune role is its effect on vaccine responses. Spiegel et al. (2002) vaccinated subjects against hepatitis B and monitored antibody titers:
| Sleep Duration | Antibody Response |
|---|---|
| ≥7 hours | Full protective titer |
| <6 hours | ~11.5× lower antibody titer |
By 6 months, 50% of sleep-restricted subjects had non-protective titers, compared to <10% of normal sleepers. This suggests sleep deprivation in the days surrounding vaccination (before and after) substantially impairs the acquired immune response.
Cohen et al. (2009) replicated this finding with influenza vaccination, demonstrating that individuals sleeping <6 hours in the 5 days post-vaccination had 4× lower antibody titers at 1 month and were significantly more likely to have non-protective responses.
Natural Killer Cells
NK cells are innate immune cells that destroy virally infected cells and cancer cells without prior sensitization. Irwin et al. (1994) demonstrated that just one partial night of sleep deprivation (subjects kept awake 0–3am, allowed to sleep at 3am) reduced NK cell activity by 28% the following morning.
More severe deprivation produces proportionally greater NK suppression. Chronic sleep restriction maintains NK suppression — a potential mechanism linking chronic short sleep to increased infection susceptibility and cancer risk.
Epidemiological Evidence
Population studies confirm the mechanistic findings:
- Sleeping ≤6h associated with 4× higher cold susceptibility (Cohen et al., 2009)
- Night shift workers (circadian disruption + sleep restriction) show 50% increased cancer risk in some studies
- Insufficient sleep is an independent risk factor for upper respiratory tract infections in children and adults
Related Pages
Sources
- Irwin M et al. — Partial night sleep deprivation reduces natural killer and cellular immune responses in humans. FASEB J (1994)
- Spiegel K et al. — Effect of sleep restriction on vaccine antibody responses. JAMA (2002)
- Prather AA et al. — Behaviorally assessed sleep and susceptibility to the common cold. Sleep (2015)
- Born J et al. — Effects of sleep and circadian rhythm on human circulating immune cells. J Immunol (1997)
Frequently Asked Questions
How does sleep affect the immune system?
Sleep is an active immunological state: NREM sleep triggers release of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β), promotes natural killer cell activity, and facilitates T-cell trafficking to lymph nodes for immune surveillance. Sleep deprivation suppresses NK cells, impairs vaccine responses, and increases susceptibility to respiratory infections. The interaction is bidirectional: cytokines (particularly IL-1 and TNF) also promote sleep.
Can you catch a cold from not sleeping enough?
Yes, directly demonstrated. Prather et al. (2015) exposed 164 healthy volunteers to nasal drops containing rhinovirus (common cold). Those sleeping <7h were 3× more likely to develop an actual cold than those sleeping ≥8h, after controlling for age, BMI, stress, and other factors. This is among the strongest causal evidence for sleep's role in immune defense.