Acute sleep deprivation impaired the early immune response to H1N1 virus in males, despite prolonged periods of sleep recovery after antigen exposure. In contrast, in females, the production of antibodies specific for the swine flu virus was not influenced by sleep loss. These results underline the relevance of sleep for supporting immune functions [3
Our results suggest that acute sleep deprivation is associated with a delayed induction of adaptive immune response to H1N1 virus in males that is consistent with previous data. That is, interrupted sleep at the time of first virus exposure is followed by a slower increase in specific antibody titers relative to that following undisturbed sleep [1
]. Factors important for an effective adaptive immune response show very concordant changes under sleep deprivation [4
]. For instance, the production of growth hormone normally peaks during early sleep periods [7
], and this effect is suppressed by sleep deprivation [8
]. This hormone stimulates immune function directly in that many immune cells possess receptors for growth hormone [9
]. Further, the secretion of cytokines involved in the adaptive immune response is downregulated by sleep loss (e.g. Interleukin-2 and Interleukin-7; [10
]). Such hormonal changes associated with interrupted sleep might have contributed to the decelerated immune response to H1N1 that was observed in males but not females in our study. Interestingly, in a recently published study, a lipopolysaccharide-induced immune response following acute sleep loss has been shown to induce distinct sex differences inasmuch as sleep-deprived females showed increased production of proinflammatory cytokines compared to response in sleep-deprived males [12
]. However, there are also other candidate mechanisms that may account for the impaired antibody titer response in sleep-deprived males seen on day 5. For instance, compared with sleep, sleep loss is associated with a striking decrease in the number of myeloid dendritic cell precursors [13
]. These cells play a major role for the initiation of adaptive immune responses [14
]. Further it might be that the impaired effect of sleep loss on the early antibody titer response to the H1N1 vaccination was due to a delayed migration of antibody titer producing B cells into the blood.
At the first glance, the clinical relevance of our findings is somewhat questionable because the only difference in specific antibody titers is 5 days after vaccination in males only and titers even out thereafter, which in the end results in same possible protection in sleep deprived and regular sleep subjects. In contrast, other studies with a similar study design showed profound effects of sleep deprivation on specific antibody titers at later time points, e.g. a 2-fold higher hepatitis A titer at day 28 post immunization in regular sleep subjects as compared to sleep deprived men [2
]. Nevertheless, in a sort of external validation of our results, previous observations revealed that partial sleep deprivation in the time of vaccination against a seasonal influenza virus induced differences in specific antibody titers during early periods (ie., after 10 days) but not during late periods (ie., after 28 days) of the adaptive immune response [1
]. One explanation for the discrepancy in results among these studies could be that the effect size of sleep deprivation on adaptive immune responses is antigen- specific.