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Tanja Lange

Publications and source records attributed to Tanja Lange.

7 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↗
PubMed2002

Systemic immune parameters and sleep after ultra-low dose administration of IL-2 in healthy men.

A somnogenic function is suspected for various cytokines. Foregoing experiments in humans indicated a selective increase in the production of interleukin-2 (IL-2) during sleep as compared with nocturnal wakefulness. Here, we examined whether conversely, IL-2 exerts a promoting influence on sleep. Also, the effects of IL-2 administered at ultra-low doses on systemic immune and endocrine parameters were assessed. Eighteen healthy men participated in three night sessions, receiving subcutaneously at 19:00 h either placebo or recombinant human IL-2 at doses of 1000 and 10,000 IU/kg bw. Polysomnographical recordings were obtained between 23:00 and 07:00 h. Blood was collected repeatedly to determine (i) white blood cell (WBC) counts including the enumeration of monocytes, natural killer (NK) cells, and lymphocyte subsets, (ii) serum concentrations of IL-2, soluble IL-2 receptor (sIL-2r), IL-4, IL-6, and interferon-gamma (IFN-gamma), and (iii) concentrations of adrenocorticotropin (ACTH), cortisol, thyreotropin (TSH), and growth hormone (GH). Changes after 1000 IU/kg bw IL-2 generally remained non-significant. However, distinct effects occurred after 10,000 IU/kg bw IL-2, inducing serum IL-2 concentrations selectively activating the high affinity IL-2 receptor. At this dose, IL-2 reduced the number of circulating lymphocytes (including all major subtypes) and NK cells, while counts of monocytes and neutrophils were increased. IL-4 release was stimulated and IFN-gamma concentration reduced after IL-2. Also, IL-2 increased the TSH concentration. There were no hints at a sleep promoting effect of IL-2. Immune changes suggest that nocturnal IL-2 administration induces a shift towards Th2 mediated defense.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Sleep enhances the human antibody response to hepatitis A vaccination.

OBJECTIVE: The common belief that sleep supports immune defense has received surprisingly little direct experimental support. The antibody response to vaccination provides a valid tool to assess the influence of sleep on adaptive immune functioning in humans, which is also clinically relevant. METHODS: Two groups of healthy humans (N = 19) not previously infected with hepatitis A virus (HAV) were studied. On the night after primary vaccination with inactivated HAV, which took place at 0900 hours, one group had regular sleep. The other group stayed awake, and did not sleep before 2100 hours the following day. HAV antibody titers were measured repeatedly until 28 days after vaccination. Plasma hormone concentrations and white blood cell (WBC) subset counts were determined on the night and day after vaccination. RESULTS: Subjects who had regular sleep after vaccination, displayed a nearly two-fold higher HAV antibody titer after 4 weeks than subjects staying awake on this night (p=.018). Compared with wakefulness, sleep after vaccination distinctly increased release of several immune-stimulating hormones including growth hormone, prolactin, and dopamine (p <.01). Concentrations of thyrotropin, norepinephrine, and epinephrine were lowered by sleep (p <.02), whereas sleep only marginally influenced WBC subset counts. CONCLUSIONS: Data suggest that sleep compared with sleep deprivation on the night after vaccination improves the formation of antigen-specific immune defense as reflected by antibody production in humans. Sleep presumably acts by inducing a hormonal environment in secondary lymphoid tissues, enhancing lymphocyte proliferation and differentiation and finally antibody synthesis. Results underscore the importance of sleep for immunocompetence.

Adult↗