Towards the therapeutic use of intranasal neuropeptide administration in metabolic and cognitive disorders.

The nose provides an effective way for delivering neuropeptides to the central nervous system, bypassing the blood-brain barrier and avoiding systemic side effects. Thereby intranasal neuropeptide administration enables the modulation of central nervous signaling pathways of body weight regulation and cognitive functions. Central nervous control of energy homeostasis is assumed to rely on hypothalamic neuropeptidergic pathways that are triggered by the peripheral adiposity signals insulin and leptin conveying the amount of body fat to the brain.

To dip or not to dip: on the physiology of blood pressure decrease during nocturnal sleep in healthy humans.

That sleep is accompanied by a blood pressure decrease is well known; however, the underlying physiology deserves further investigation. The present study examines in healthy subjects 2 main questions: is this dipping actively evoked? and what are the consequences of nondipping for daytime blood pressure? Nocturnal blood pressure was extrinsically elevated in 12 sleeping subjects to mean daytime values by continuously infused phenylephrine. This nondipping significantly lowered morning blood pressure during rest and 3 hours after resuming physical activity compared with a control condition (isotonic saline).

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.

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.

Differential effects of hydrocortisone on sympathetic and hemodynamic responses to sympathoexcitatory manoeuvres in men.

Aim of the present study was to investigate the influence of hydrocortisone on muscle sympathetic nerve activity (MSNA) and hemodynamic parameters during different sympathoexcitatory manoeuvres in humans. The study focuses on the interaction of the hypothalamo-pituitary-adrenal system and the sympathetic nervous system. Hydrocortisone 100 mg or placebo was administered intravenously to eight young healthy subjects in a double-blind crossover design.

Intranasal insulin reduces body fat in men but not in women.

Insulin acts in the central nervous system to reduce food intake and body weight and is considered a major adiposity signal. After intranasal administration, insulin enters the cerebrospinal fluid compartment and alters brain functions in the absence of substantial absorption into the blood stream. Here we report the effects of 8 weeks of intranasal administration of insulin (4 x 40 IU/day) or placebo to two groups of healthy human subjects (12 men and 8 women in each group).

Manipulating central nervous mechanisms of food intake and body weight regulation by intranasal administration of neuropeptides in man.

Maintaining a stable body weight set-point is assumed to rely on a homeostatic central nervous system (CNS) regulation of body fat with the particular involvement of hypothalamic pathways. The peripheral adiposity signals insulin and leptin convey information on the amount of energy stored as body fat to the arcuate nucleus of the hypothalamus, where anabolic/orexigenic and catabolic/anorexigenic pathways interact to regulate food intake and energy expenditure. One of the most prominent orexigenic messengers is neuropeptide Y (NPY), whereas melanocortins, including alpha-melanocyte-stimulating hormone (alpha-MSH), are essential for inducing anorexigenic effects.

Intranasal atrial natriuretic peptide acts as central nervous inhibitor of the hypothalamo-pituitary-adrenal stress system in humans.

Increased hypothalamo-pituitary-adrenal activity contributes to morbidity in widespread metabolic and psychiatric diseases. Inhibition of hypercortisolism represents a promising therapeutic strategy in these conditions, which currently cannot be used. Here, we tested the hypothesis that atrial natriuretic peptide (ANP) administered intranasally is a safe and feasible inhibitor of pituitary-adrenal activity at the central nervous level.

Improvement of sleep and pituitary-adrenal inhibition after subchronic intranasal vasopressin treatment in elderly humans.

Subchronic intranasal treatment with argininevasopressin (AVP) has been shown to exert a strong ameliorating effect on sleep and slow wave sleep (SWS) deficits in elderly. However, AVP is also a potent stimulus of the pituitary-adrenal stress system, which is usually inhibited during early, SWS-rich sleep. A disinhibition of pituitary-adrenal activity during sleep is correlated with aging and is considered a pathologic factor contributing to various age-related diseases.

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.

Growth hormone-releasing hormone facilitates hypoglycemia-induced release of cortisol.

Early sleep in humans is characterized by a distinct suppression of pituitary-adrenal activity coinciding with enhanced activity of the somatotropic axis. Here, we tested in awake humans the hypothesis of an inhibiting influence of hypothalamic growth hormone-releasing hormone (GHRH) on pituitary-adrenal activity. For this purpose, pituitary-adrenal activity was stimulated in 10 men through a standard insulin-hypoglycemia-test (IHT) and in another 10 men through combined administration of CRH/vasopressin.