Biomedical subjects

Stoyan Dimitrov

Publications and source records attributed to Stoyan Dimitrov.

4 recordsLinked to original sources

PubMed2006

Shift of monocyte function toward cellular immunity during sleep.

BACKGROUND: Sleep is considered to strengthen immune defense. We hypothesized that sleep achieves this effect by shifting the balance between types 1 and 2 cytokine activity toward increased type 1 activity, thereby supporting adaptive cellular immune responses. METHODS: We analyzed monocyte-derived type 1 (interleukin 12 [IL-12]) and type 2 (IL-10) cytokines by means of multiparametric flow cytometry in healthy human subjects (n = 11) during a regular sleep-wake cycle and 24 hours of wakefulness. RESULTS: Sleep increased the number of IL-12-producing monocytes and concurrently decreased the number of IL-10-producing monocytes, thereby inducing clear rhythms in these cells, with maximum numbers at 2:20 and 11:30 am, respectively. The rhythms were completely absent during continuous wakefulness. Correlation analyses and supplementary in vitro studies suggest that high prolactin and low cortisol levels are factors contributing to the shift in the IL-12/IL-10 ratio toward increased IL-12 activity during sleep. CONCLUSIONS: Monocyte-derived IL-12 and IL-10 play a critical role for tuning the synapse between antigen-presenting cells and lymphocytes. By preferentially supporting type 1 IL-12 activity, sleep induces a 24-hour oscillation between predominant types 1 and 2 cytokines and, in this way, acts to globally increase the efficacy of adaptive immune responses. Improving sleep could represent a therapeutic option to enhance the success of vaccinations and success in the treatment of diseases (eg, atopic dermatitis and human immunodeficiency virus infection) that are characterized by type 2 cytokine overactivity.

Adult↗

PubMed2006

Sleep enhances IL-6 trans-signaling in humans.

Sleep is commonly considered to support immune defense. The underlying sleep-immune interaction appears to rely critically on cytokines, like interleukin-6 (IL-6), that combine effects on immune and neuronal functions. The IL-6 signal is conveyed in two ways: it stimulates a restricted group of (mostly immune) cells via membrane-bound IL-6 receptors (mIL-6R) by forming a complex with soluble IL-6R (sIL-6R), and it stimulates (via membrane-bound gp130) a great variety of other cell types--a process termed trans-signaling. Focusing on the receptor side of IL-6 signaling, we examined the effect of sleep on sIL-6R plasma concentrations, mIL-6R expression, plasma sgp130, and numbers of IL-6-producing monocytes in healthy humans who were tested during a regular sleep-wake cycle and 24 h of wakefulness while blood was sampled repeatedly. Sleep strongly enhanced concentrations of sIL-6R, exceeding wake levels by 70% at the end of sleep. This rise was due to an increase in the PC (proteolytic cleavage) rather than the DS (differentially spliced) variant of sIL-6R. Sleep did not affect IL-6-producing monocytes, mIL-6R density, or sgp130 concentrations. The selective increase in sIL-6R implicates an enhanced trans-signaling capacity whereby sleep distinctly widens the profile of IL-6 actions, enabling an integrated influence on brain and peripheral organs.

Adult↗

PubMed2005

Sleep-like concentrations of growth hormone and cortisol modulate type1 and type2 in-vitro cytokine production in human T cells.

Slow wave sleep (SWS) is characterized by maximum release of growth hormone (GH) and minimum release of cortisol. We hypothesized that this hormonal pattern during SWS leads, in addition to generally increased T cell cytokine production, to a shift towards type1 cytokines. To test this hypothesis, blood was sampled from 8 humans during SWS, and whole blood cultures were activated in-vitro with ionomycin and phorbol-myrestate-acetate (PMA) in the absence and presence of GH neutralizing antibody (Ab) or physiological concentrations of cortisol. Production of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-4, and tumor necrosis factor-alpha (TNF-alpha) was measured using multiparametric flow cytometry. GH Ab decreased IFN-gamma+CD4+ cells but had no effect on other cytokines. Cortisol alone and in combination with GH Ab decreased CD4+ and CD8+ cells producing IFN-gamma, TNF-alpha and IL-2. Simultaneously, these two reactants reduced IL-4+CD4+ cells, so that the ratio of IFN-gamma/IL4 producing CD4+ cells indicated an unexpected shift towards type1 dominance. Results support the view that release of GH by increasing particularly production of IFN-gamma can contribute to the shift in type1/type2 balance towards type1 activity characterizing SWS. Suppression of cortisol during this sleep period enhances both type1 and type2 activity. Yet, our finding of predominant type1 activity after cortisol administration, rules out any relevance of this suppression for the shift towards type1 activity during SWS.

Adult↗

PubMed2004

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 07:00 h) and while remaining awake during the same nocturnal interval, in a within-subject cross-over design. Blood was collected every 2 h. Production of T cell derived cytokines--interferon-gamma (IFN-gamma), interleukin-2 (IL-2), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-alpha)--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-gamma/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-alpha producing CD8+ cells probably reflecting increased extravasation of cytotoxic effector and memory T cells.

Adult↗