Biomedical subjects

Reiner Oberbeck

Publications and source records attributed to Reiner Oberbeck.

11 recordsLinked to original sources

PubMed2006

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. METHODS: Male NMRI-mice were subjected to sham operation or to sepsis (caecal ligation and puncture, CLP) following administration of either the non-selective beta-adrenergic antagonist propranolol (0.5 mg/kg s.c. every 12 h in 1 ml vehicle) or saline 0.9% (1 ml s.c. every 12 h). Mice were kept in metabolic cages and were sacrificed 48 h after induction of sepsis. Survival rate, clinical situation (body weight and temperature, fluid and food intake, urine output), and immunological variables (splenocyte proliferation, apoptosis, and IFN-gamma and IL-6 release) were determined. RESULTS: Administration of propranolol in septic mice increased the splenocyte apoptosis rate, reduced the proliferative capacity of splenocytes, and modulated cellular cytokine release (IL-6, IFN-gamma). This was paralleled by a higher loss of body weight and temperature, and a decreased urine output. Furthermore, treatment with propranolol increased the sepsis-induced lethality from 47% up to 68%, respectively. CONCLUSION: beta-Adrenergic blockade was accompanied by alterations of cellular immune functions, a deterioration in the clinical situation and a reduced survival in a murine model of sepsis. These data demonstrate the potential immuno-modulatory effects of beta-adrenergic antagonists.

Adrenergic beta-Antagonists↗

PubMed2006

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. INTERVENTIONS: Mice were subjected to laparotomy (sham intervention, LAP) or polymicrobial sepsis induced by cecal ligation and puncture (CLP). Mice in each of these conditions received either an intraperitoneal infusion of 0.9% saline (CLP/saline; LAP/saline) or an intraperitoneal infusion of dopamine (1.0 microg/kg/min i.p., CLP/DOP; LAP/DOP). Metabolic data and survival were monitored 24 h and 48 h after onset of sepsis, and animals were terminated 48 h after induction of sepsis to determine splenocyte apoptosis (Annexin V binding capacity), splenocyte proliferation (3H-Thymidine incorporation assay), splenocyte IL-2, IL-6 and IFN-gamma release (ELISA) and leukocyte distribution (WBC; CD3, CD4, CD8, B220, F4/80, NK1.1). MEASUREMENTS AND RESULTS: Infusion of dopamine in septic mice increased splenocyte apoptosis and decreased splenocyte proliferation and IL-2 release of septic mice. Furthermore, an inhibitory effect of dopamine infusion on splenocyte proliferation and the release of the TH1-cytokines IL-2 and IFN-gamma was observed in sham operated control mice. These effects were paralleled by a decreased survival of dopamine-treated septic animals (47% vs. 67%). Treatment with DOP did not affect sepsis-induced changes of leukocyte distribution. CONCLUSIONS: We conclude that dopamine is capable of modulating cellular immune functions in a murine model of sepsis.

Animals↗

PubMed2006

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. To further elucidate the physiological significance of these interactions, investigators tried to reveal the importance of the catecholaminergic modulation of the immune system under pathological conditions like hemorrhagic shock and systemic inflammation, since catecholamines and adrenergic antagonists are frequently used drugs in the treatment of the critically ill. Furthermore, the interaction between catecholamines and the immune system is supposed to be an important factor in the development of autoimmune diseases and may influence their progress. In addition to the effects of peripheral circulating catecholamines, it was demonstrated that catecholamines that are released within the central nervous system may profoundly influence the activity of the peripheral immune system. Starting with a short historical overview over the immunomodulatory effects of blood catecholamines under good health conditions during critical illness and during autoimmune disease will be reviewed and the immunomodulatory effects of centrally released catecholamines will be discussed.

Animals↗

PubMed2004

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. Sepsis (CLP) was induced in male NMRI mice that received either 0.9% saline, dopexamine (0.05 mg/kg/hour ip, DPX), the selective beta2-adrenergic antagonist ICI 118.551 (0.5 mg/kg ip every 12 hours, ICI) or a combination of both drugs. 48 hours after onset of sepsis, survival rate, splenocyte apoptosis, splenocyte proliferation, splenocyte IL-2, IL-6 and IFN-gamma release, and leukocyte distribution were monitored. Dopexamine increased splenocyte apoptosis and normalized the distribution of circulating lymphocytes but did not affect sepsis-induced mortality. ICI 118.551 induced a dramatic increase of mortality paralleled by a decreased splenocyte proliferation and the strongest increase in splenocyte apoptosis. Co-administration of dopexamine abolished the ICI 118.551-induced alterations but this effect seemed to be mediated via a pathway other than adrenergic beta2-receptors. We conclude that dopexamine modulates cellular immune functions during systemic inflammation and that different receptor systems are involved in the mediation of this process. Furthermore, the immunomodulatory effect of beta2-adrenergic blockade was demonstrated.

Adrenergic beta-Antagonists↗

PubMed2004

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. In the intervention group, specified topics for every session, a course book describing only those procedures relevant for the course and a foregoing case-based active learning session were introduced as compared to the traditional way of teaching the surgical examination course. For evaluation a questionnaire for the students was used. A total of 614 questionnaires (return rate 79.6%) were included in the analysis. Student as well as teacher preparation significantly improved in the intervention group from 34.8 to 73.6% and 46.1 to 73.0%, respectively. The case-based learning session and the course book were considered helpful by 77.7 and 96.4% of the students, respectively. The introduction of a timetable with specified topics for every session, a course book and a foregoing case-based learning session significantly improved student preparation for the surgical clinical examination course.

Competency-Based Education↗

PubMed2004

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 (0.05 mg/kg/h i.p.), administration of the nonselective beta-adrenoceptor antagonist propranolol (0.5 mg/kg s.c.), or a combination of epinephrine and propranolol after induction of a polymicrobial sepsis by cecal ligation and puncture. Forty-eight hours thereafter survival and cellular immune functions (splenocyte proliferation, splenocyte apoptosis and cytokine release, distribution of leukocyte subsets) were determined. RESULTS: Infusion of epinephrine did not affect lethality of septic mice but induced alterations of splenocyte apoptosis, splenocyte proliferation and IL-2 release and was associated with profound changes of circulating immune cell subpopulations. Treatment with propranolol augmented the epinephrine-induced increase of splenocyte apoptosis, did not affect the decrease of splenocyte proliferation and IL-2 release, augmented the release of IL-6 and antagonized the mobilization of natural killer cells observed in epinephrine-treated animals. Furthermore, these immunologic alterations were accompanied by a significant increase of sepsis-induced mortality. Coadministration of propranolol and epinephrine augmented the propranolol-induced changes of splenocyte apoptosis and IL-6 release and was associated with the highest mortality of septic mice. CONCLUSION: Epinephrine infusion modulated cellular immune functions during systemic inflammation without an impact on survival. A pharmacologic beta-adrenergic blockade partly augmented the epinephrine-induced immune alterations and was associated with a pronounced increase of mortality. This effect was further augmented by a combination of epinephrine infusion and beta-adrenergic blockade. These data indicate that adrenergic mechanisms modulate cellular immune functions and survival during sepsis, with these effects being mediated via alpha- and beta-adrenergic pathways.

Adrenergic beta-Antagonists↗

PubMed2004

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. Apart of the glucocorticoids several hormones and neurotransmitters released by these systems are capable of altering immune functions. This includes the catecholamines epinephrine, norepinephrine and dopamine, the pituitary hormone prolactin, and the adrenal hormone dehydroepiandrosterone (DHEA). Several pathological states are paralleled by an activation of the endocrine system leading to an increased hormone release. In line with this an elevated release of catecholamines, of prolactin, and of DHEA has been demonstrated after major surgery, during systemic inflammation and following trauma hemorrhage. Furthermore, due to their pharmacologic properties several neurotransmitters are used as pharmaceutical agents to stabilize cardiovascular function or to prevent organ failure (e.g. epinephrine, norepinephrine, dopamine). Several pharmacological substances interact with the release of immunomodulatory hormones (e.g. metoclopramid and prolactin, dopamine and prolactin) and some hormones are available as over-the counter self medications like DHEA. Therefore, alterations of the serum concentrations of these hormones may affect the immunocompetence of the organism and may thereby affect the clinical course of critically ill patients. The clinical and pharmacological implications of this complex relationship between the endocrine and the immune system will be provided on the background of a review of the recent literature and of our research work.

Adjuvants, Immunologic↗

PubMed2003

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. MATERIALS AND METHODS: Male NMRI mice were subjected to laparotomy (LAP) or sepsis induced by cecal ligation and puncture (CLP). Mice were treated with either saline (LAP/saline; CLP/saline) or prolactin (LAP/PRL, CLP/RPL; 4 mg/kg s.c.). Survival of septic mice was determined 24 and 48 h after CLP. Forty-eight hours after the septic challenge, the proliferative capacity, cytokine release (IL-2, IL-6, IFN-gamma) and apoptosis of splenocytes were determined. Additionally, monitoring of circulating leukocyte distribution was performed (WBC; CD3+, CD4+, CD8+, B220+, NK1.1+, F4/80+ cells by FASCan). RESULTS: CLP was accompanied by a mortality of 47% and induced a decrease in splenocyte proliferation and apoptosis rate. Administration of prolactin significantly increased the mortality of septic mice (81%). This was paralleled by a further decrease of splenocyte proliferation and an increased splenocyte apoptosis. In addition, administration of prolactin augmented the sepsis-induced inhibition of IL-2 release, attenuated the sepsis-induced inhibition of IFN-gamma release, and did not affect the release of IL-6. However, prolactin did not affect the sepsis-induced changes of circulating leukocyte subpopulations. CONCLUSIONS: We conclude that prolactin has profound immunomodulatory properties and that administration of prolactin in pharmacological doses is associated with a decreased survival and an inhibition of cellular immune functions in septic mice.

Animals↗

PubMed2003

Pavlovian conditioning of endotoxin-tolerance in rats.

The most fascinating example of the bi-directional interaction between the central nervous system (CNS) and immune system is the behavioral conditioning of immune functions. We therefore investigated the behavioral conditioning of lipopolysaccharide (LPS)-induced endotoxin tolerance using the taste aversion paradigm. The conditioned stimulus (CS) saccharin was paired with the unconditioned stimulus (UCS) LPS over a five (CONDl) or four (COND2) days learning trial. Controls received drinking water with (SHAM) or without (UNT) LPS. Endotoxin tolerance was tested by determination of LPS-induced tumor necrosis factor (TNF)-alpha release. After the avoidance of the induced endotoxin-tolerance the CS saccharin was re-presented in all experimental groups. A the end of the re-exposure period a complete endotoxin tolerance was noticed in the CONDl- and COND2-group. In contrast, no effect of saccharin administration was observed in the SHAM- or UNT-group. Our data demonstrate for the first time the behavioral conditioning of endotoxin tolerance. Furthermore, these results contribute new aspects to the mechanisms underlying the development and modulation of endotoxin tolerance.

Animals↗

PubMed2002

The effect of dehydroepiandrosterone on hemorrhage-induced suppression of cellular immune function.

OBJECTIVE: To determine whether the steroid hormone dehydroepiandrosterone (DHEA) improves cellular immune functions after hemorrhagic shock. DESIGN AND SETTING: Prospective controlled study in a research laboratory at an university medical center. SUBJECTS: Male NMRI mice. INTERVENTIONS: Animals received 0.9% saline or DHEA (20 mg/kg subcutaneously) before induction of a volume-controlled hemorrhagic shock (55% of estimated circulating blood volume) by retro-orbital puncture. One hour after hemorrhage mice underwent fluid resuscitation by intravenous infusion of lactated Ringer's solution (300% of the shed blood). Separate groups of mice were killed to obtain whole blood and spleen 1 h after hemorrhage, 1 h after fluid resuscitation, and 24 h after hemorrhage to determine lymphocyte distribution (CD4(+), CD8(+), NK1.1-AG(+)), splenocyte apoptosis, and plasma concentrations of tumor necrosis factor-alpha and interleukin-10. MEASUREMENTS AND RESULTS: Hemorrhage in control mice was associated with a rapid increase in circulating NK cell numbers. Elevated splenocyte apoptosis, an increased CD4/CD8 ratio, and decreased number of circulating CD8(+) T-cells was observed 24 h after hemorrhagic shock. DHEA administration was accompanied by a normalization of splenocyte apoptosis and lymphocyte migration. Induction of hemorrhagic shock did not affect TNF-alpha or IL-10 plasma concentrations in either treatment group. CONCLUSIONS: DHEA administration improves cellular immune function after hemorrhage and may therefore be beneficial in patients with hemorrhagic shock.

Animals↗

PubMed2002

Influence of beta-adrenoceptor antagonists on hemorrhage-induced cellular immune suppression.

Hemorrhagic shock is associated with increasing catecholamine plasma concentrations. Plasma catecholamines are known to affect cellular immune functions. We therefore, investigated the effect of endogenously released catecholamines on lymphocyte distribution (CD4+ lymphocytes, CD8+ lymphocytes, and natural killer (NK) cells), splenocyte apoptosis (Annexin V binding), tumor necrosis factor-alpha (TNF-alpha), and interleukin 10 (IL-10) release during a volume-controlled hemorrhagic shock in mice. Mice received either saline (HEM), the non-selective beta-adrenoceptor antagonist propranolol (PROP; 2 mg/kg i.p.), or the beta1-adrenoceptor antagonist metoprolol (MET; 2 mg/kg i.p.) before induction of hemorrhage. Mice were sacrificed to obtain the spleen and whole blood 1 h after hemorrhage, 1 h after fluid resuscitation, and 24 h after hemorrhage. Flow cytometric analysis revealed an increase in circulating NK cells in the HEM group. This effect was completely abolished by pretreatment with propranolol or metoprolol. Furthermore, administration of either beta-adrenoceptor antagonist led to a decrease of circulating CD8+ lymphocyte numbers. Monitoring of splenocyte apoptosis by determination of Annexin V binding revealed an increase in splenocyte apoptosis 24 h after hemorrhage in the HEM group but not in the animals pretreated with propranolol or metoprolol. Induction of hemorrhage did not affect TNF-alpha or IL-10 plasma concentrations in either experimental group. We conclude that plasma catecholamines affect cellular immunity in the early phase of trauma via a beta-adrenergic pathway.

Adrenergic beta-1 Receptor Antagonists↗