Sleep associated regulation of T helper 1/T helper 2 cytokine balance in humans

Recent human studies suggested a supportive influence of regular nocturnal sleep on immune responses to experimental infection (vaccination). We hypothesized here that sleep could ease such responses by shifting the balance between T helper 1 (Th1) and T helper 2 (Th2) cytokine activity towards Th1 dominance thereby favoring cellular over humoral responses to infection. We compared the Th1/Th2 cytokine balance in 14 healthy men during regular nocturnal sleep (between 23:00 and 07:00h) and while remaining awake during the same nocturnal interval, in a within-subject cross-over design. Blood was collected every 2h. Production of T cell derived cytokines - interferon-γ (IFN-γ), interleukin-2 (IL-2), interleukin-4 (IL-4), and tumor necrosis factor-α (TNF-α) - was measured at the single cell level using multiparametric flow cytometry. Also, several immunoactive hormones - prolactin, growth hormone (GH), thyroid stimulating hormone (TSH), cortisol, and melatonin - were measured, the release of which is known to be regulated by sleep. Compared with wakefulness, early nocturnal sleep induced a shift in the Th1/Th2 cytokine balance towards increased Th1 activity, as indicated by an increased (p<.05) ratio of IFN-γ/IL-4 producing T helper cells. However, the Th1 shift was only of moderate size and replaced by Th2 dominance during late sleep (p<.05). It could be mediated via release of prolactin and GH which both were distinctly increased during sleep (p<.001). Though unexpected, the most pronounced effect of sleep on T cell cytokine production was a robust decrease in TNF-α producing CD8+ cells probably reflecting increased extravasation of cytotoxic effector and memory T cells.