Neuroendocrine Modulation of the Immune Response after Trauma and Sepsis: Does It Influence Outcome?

Although the treatment of multiple-injured patients has been improved during the last decades, sepsis and multiple organ failure (MOF) still remain the major cause of death. Following trauma, profound alterations of a large number of physiological systems can be observed that may potentially contribute to the development of sepsis and MOF. This includes alterations of the neuroendocrine and the immune system.

Low dose LPS does not increase TLR4 expression on monocytes in a human in vivo model.

Background And Purpose: Toll like receptor 4 (TLR4) is the major recognition receptor for lipopolysaccharides and plays a major role in the inflammatory response. CD11b is expressed on the surface of many leukocytes including monocytes. The CD11b/CD18 complex is involved in the inflammatory response by mediating migration and adhesion of leukocytes.

Experimental human endotoxemia enhances brain activity during social cognition.

Acute peripheral inflammation with corresponding increases in peripheral cytokines affects neuropsychological functions and induces depression-like symptoms. However, possible effects of increased immune responses on social cognition remain unknown. Therefore, this study investigated the effects of experimentally induced acute inflammation on performance and neural responses during a social cognition task assessing Theory of Mind (ToM) ability.

Androstenediol modulates sepsis induced alterations of survival and immune functions in a murine model of sepsis.

Background: Recently the benefit of subcutaneously applied dehydroepiandrosterone (DHEA) during sepsis was demonstrated. It was therefore supposed that the impact of DHEA might be induced by its metabolite androstenediol produced via conversion in subcutaneous tissue. Thus we postulate a comparable impact of intravenously applied androstenediol like DHEA.

Salivary α-amylase response to endotoxin administration in humans.

Salivary α-amylase (sAA) is a digestive enzyme that plays also an important role in mucosal immunity. Secretion of the sAA is largely under the control of the autonomic nervous system and increases in sAA activity have repeatedly been observed in response to various stressors. The present study aimed at investigating whether and to what extent sAA activity levels are affected during systemic inflammation.

Neural response to emotional stimuli during experimental human endotoxemia.

Increases in peripheral cytokines during acute inflammation may affect various neuropsychological functions. The aim of this functional magnetic resonance imaging (fMRI) study was to investigate the effects of acute endotoxemia on mood and the neural response to emotionally aversive visual stimuli in healthy human subjects. In a double-blind, randomized crossover study, 18 healthy males received a bolus injection of bacterial lipopolysaccharide (LPS; 0.

Acute experimental endotoxemia induces visceral hypersensitivity and altered pain evaluation in healthy humans.

Growing evidence suggests that systemic immune activation plays a role in the pathophysiology of pain in functional bowel disorders. By implementing a randomized crossover study with an injection of endotoxin or saline, we aimed to test the hypothesis that endotoxin-induced systemic inflammation increases visceral pain sensitivity in humans. Eleven healthy men (mean ± standard error of the mean age 26.

Dose-dependent effects of endotoxin on neurobehavioral functions in humans.

Clinical and experimental evidence document that inflammation and increased peripheral cytokine levels are associated with depression-like symptoms and neuropsychological disturbances in humans. However, it remains unclear whether and to what extent cognitive functions like memory and attention are affected by and related to the dose of the inflammatory stimulus. Thus, in a cross-over, double-blind, experimental approach, healthy male volunteers were administered with either placebo or bacterial lipopolysaccharide (LPS) at doses of 0.

Single-trial conditioning in a human taste-endotoxin paradigm induces conditioned odor aversion but not cytokine responses.

Immunological responses to bacterial endotoxin can be behaviorally conditioned in rodents. However, it is unclear whether an acute systemic inflammatory response can be behaviorally conditioned in humans. Thus, in a double-blind placebo-controlled study, 20 healthy, male subjects received either a single injection of lipopolysaccharide (LPS) or saline together with a novel tasting beverage (conditioned stimulus, CS).

Lipopolysaccharide-induced experimental immune activation does not impair memory functions in humans.

Systemic immune activation occurring together with release of peripheral cytokines can affect behavior and the functioning of the central nervous system (CNS). However, it remains unknown whether and to what extent cognitive functions like memory and attention are affected during transient immune activation. We employed a human endotoxemia model and standardized neuropsychological tests to assess the cognitive effects of an experimental inflammation in two groups of 12 healthy young men before and after intravenous injection of lipopolysaccharide (LPS, Escherichia coli, 0.

Dehydroepiandrosterone modulates survival and immune functions during sepsis depending on the way of drug administration.

Background: Administration of dehydroepiandrosterone (DHEA) has been demonstrated to improve survival and cellular immune functions during systemic inflammation. Although there is evidence that the route of drug application may profoundly affect the DHEA-induced effects the impact of this parameter remains to be established.

Materials And Methods: Male NMRI mice were subjected to sham-operation (laparotomy) or sepsis (cecal ligation and puncture).

Dehydroepiandrosterone during sepsis: does the timing of administration influence the effectiveness.

Background: Administration of dehydroepiandrosterone (DHEA) has been demonstrated to improve survival and cellular immune functions during systemic inflammation. Although there is evidence that the time point of drug application may profoundly affect the DHEA-induced effects the impact of this parameter remains to be established.

Methods: Male NMRI mice were subjected to sham-operation (laparotomy) or sepsis (cecal ligation and puncture).

A civilian perspective on ballistic trauma and gunshot injuries.

Background: Gun violence is on the rise in some European countries, however most of the literature on gunshot injuries pertains to military weaponry and is difficult to apply to civilians, due to dissimilarities in wound contamination and wounding potential of firearms and ammunition. Gunshot injuries in civilians have more focal injury patterns and should be considered distinct entities.

Methods: A search of the National Library of Medicine and the National Institutes of Health MEDLINE database was performed using PubMed.

Beta-adrenergic antagonists: indications and potential immunomodulatory side effects in the critically ill.

Pharmacologic blockade of beta-adrenergic receptors is a frequent therapeutic intervention in critically ill patients. Today's strategies predominantly include the treatment of cardiovascular diseases like hypertension and cardiac arrhythmias. Furthermore, beta-adrenergic antagonists are routinely used to prevent the catecholamine-induced hypermetabolism in critically ill patients suffering from severe burn injury.

Microcirculatory alterations of hepatic and mesenteric microcirculation in endotoxin tolerance.

LPSs getting access to the circulation of mammalian organisms cause typical systemic inflammatory reactions with symptoms characteristic for acute sepsis. One possibility to attenuate LPS effects is to expose a host to a challenge with low LPS doses, which results in the establishment of "endotoxin tolerance" (ET). Because the microcirculation is of particular importance in LPS action, it seemed of interest to analyze leukocyte-endothelial interactions in the mesentery and liver once endotoxin tolerance has been established and are challenged with LPS.

Survival and cellular immune functions in septic mice treated with growth hormone (GH) and insulin-like growth factor-I (IGF-I).

Objective: GH was used to counteract the catabolic metabolism in critically ill patients until it was demonstrated that administration of GH was associated with an increased morbidity due to uncontrolled infections and sepsis. The immunomodulatory effect of GH and its main mediator IGF-I during systemic inflammation remain to be established. We therefore investigated the effect of GH and IGF-I on cellular immune functions in a murine model of sepsis.

Dehydroepiandrosterone: a modulator of cellular immunity and heat shock protein 70 production during polymicrobial sepsis.

Objective: DHEA is an immunomodulatory steroid hormone that improves survival during systemic inflammation. A DHEA-induced modulation of heat shock protein response may be an alternative mechanism contributing to the beneficial effects of this hormone. We investigated the effect of DHEA administration on survival, cellular immune functions, and HSP-70 production in septic mice.

beta-Adrenergic blockade during systemic inflammation: impact on cellular immune functions and survival in a murine model of sepsis.

Aim Of The Study: Adrenergic immuno-modulation mediated by beta-adrenergic receptors has been demonstrated. Pharmacological blockade of beta-adrenergic receptors is a therapeutic intervention frequently used in critically ill patients. The effect of beta-adrenergic blockade on cellular immune functions in a critical illness, such as polymicrobial sepsis, has not been investigated.

Catecholamines: physiological immunomodulators during health and illness.

The existence of an immune-endocrine interaction has been reported and the modulatory effects of the natural occurring catecholamines epinephrine, norepinephrine and dopamine as well as of pharmaceutically generated catecholamines like dopexamine on a wide variety of immune functions were demonstrated. Furthermore, it was noticed that these effects are mediated by specific adrenergic and dopaminergic receptors expressed on the surface of immunological target cells. At first, the adrenergic immunomodulation was predominantly investigated in healthy volunteers and profound immunomodulatory effects were reported for endogenously released and exogenously administered catecholamines.

Dopamine affects cellular immune functions during polymicrobial sepsis.

Objective: To determine whether infusion of dopamine modulates cellular immune functions and survival during systemic inflammation.

Design And Setting: Randomized animal study, university research laboratory, Level I trauma center.

Subjects: Male NMRI mice.

Improved student preparation from implementing active learning sessions and a standardized curriculum in the surgical examination course.

Students' knowledge before and preparation for courses with practical skills training or bedside teaching may be insufficient and reduce efficiency of teaching time at the bedside and in skills training. To study the effect of a new curriculum on students' preparation for courses, a quasi-randomized study was conducted. All medical students were included who participated in the surgical examination course during a period of four semesters.

Adrenergic modulation of survival and cellular immune functions during polymicrobial sepsis.

Objective: An immunomodulatory effect of epinephrine has been reported that is supposed to be mediated via beta-adrenergic receptors. The effect of epinephrine and/or beta-adrenergic blockade on cellular immune functions during systemic inflammation has not yet been investigated.

Methods: Male NMRI mice were treated with either an infusion of epinephrine (0.

Therapeutic implications of immune-endocrine interactions in the critically ill patients.

The existence of an immune-endocrine interaction has been demonstrated decades ago. An immunomodulatory effect was reported for a wide range of hormones. The best known example for this interaction is the glucocorticoids released by the adrenal cortex.

Dopexamine and cellular immune functions during systemic inflammation.

An immune-neuroendocrine interaction that is mediated via beta2-adrenergic receptors has been demonstrated previously. Dopexamine is a substance with strong beta2-adrenergic effects and is used in the treatment of critically ill patients. We therefore investigated the effect of dopexamine infusion on survival and cellular immune functions during systemic inflammation.

Prolactin modulates survival and cellular immune functions in septic mice.

Background: The immunomodulatory properties of the pituitary hormone prolactin have been demonstrated. It was proposed that prolactin is important in maintaining normal immune response in several pathological states. We investigated the effect of prolactin administration on the survival and cellular immune functions during systemic inflammation.