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Manfred Schedlowski

Publications and source records attributed to Manfred Schedlowski.

At least 37 records · Page 2Linked to original sources
PubMed2005

Neural substrates for behaviorally conditioned immunosuppression in the rat.

We have previously demonstrated behaviorally conditioned immunosuppression using cyclosporin A as an unconditioned stimulus and saccharin as a conditioned stimulus. In the current study, we examined the central processing of this phenomenon generating excitotoxic lesions before and after acquisition to discriminate between learning and memory processes. Three different brain areas were analyzed: insular cortex (IC), amygdala (Am), and ventromedial nucleus of the hypothalamus (VMH). The results demonstrate that IC lesions performed before and after acquisition disrupted the behavioral component of the conditioned response (taste aversion). In contrast, Am and VMH lesions did not affect conditioned taste aversion. The behaviorally conditioned suppression of splenocyte proliferation and cytokine production (interleukin-2 and interferon-gamma) was differentially affected by the excitotoxic lesions, showing that the IC is essential to acquire and evoke this conditioned response of the immune system. In contrast, the Am seems to mediate the input of visceral information necessary at the acquisition time, whereas the VMH appears to participate within the output pathway to the immune system necessary to evoke the behavioral conditioned immune response. The present data reveal relevant neural mechanisms underlying the learning and memory processes of behaviorally conditioned immunosuppression.

Amygdala↗
PubMed2005

Towards an immuno-precipitated neurodevelopmental animal model of schizophrenia.

Epidemiological studies have indicated an association between maternal bacterial and viral infections during pregnancy and the higher incidence of schizophrenia in the resultant offspring post-puberty. One hypothesis asserts that the reported epidemiological link is mediated by prenatal activation of the foetal immune system in response to the elevation of maternal cytokine level due to infection. Here, we report that pregnant mouse dams receiving a single exposure to the cytokine-releasing agent, polyriboinosinic-polyribocytidilic acid (PolyI:C; at 2.5, 5.0, or 10.0 mg/kg) on gestation day 9 produced offspring that subsequently exhibited multiple schizophrenia-related behavioural deficits in adulthood, in comparison to offspring from vehicle injected or non-injected control dams. The efficacy of the PolyI:C challenge to induce cytokine responses in naïve non-pregnant adult female mice and in foetal brain tissue when injected to pregnant mice were further ascertained in separate subjects: (i) a dose-dependent elevation of interleukin-10 was detected in the adult female mice at 1 and 6h post-injection, (ii) 12 h following prenatal PolyI:C challenge, the foetal levels of interleukin-1beta were elevated. The spectrum of abnormalities included impairments in exploratory behaviour, prepulse inhibition, latent inhibition, the US-pre-exposure effect, spatial working memory; and enhancement in the locomotor response to systemic amphetamine (2.5 mg/kg, i.p.) as well as in discrimination reversal learning. The neuropsychological parallels between prenatal PolyI:C treatment in mice and psychosis in humans, demonstrated here, leads us to conclude that prenatal PolyI:C treatment represents one of the most powerful environmental-developmental models of schizophrenia to date. The uniqueness of this model lies in its epidemiological and immunological relevance. It is, sui generis, ideally suited for the investigation of the neuropsychoimmunological mechanisms implicated in the developmental aetiology and disease processes of schizophrenia.

Animals↗
PubMed2005

Effects of mind-body therapy on quality of life and neuroendocrine and cellular immune functions in patients with ulcerative colitis.

BACKGROUND: The aim of this study was to investigate the effects of mind-body therapy on neuroendocrine and cellular immune measures, health-related quality of life and disease activity in patients with ulcerative colitis (UC) in remission. METHODS: Thirty UC patients in remission or with low disease activity were randomly assigned to an intervention group (n = 15) or a usual-care waiting control group (n = 15). Intervention consisted of a structured 60-hour training program over 10 weeks which included stress management training, moderate exercise, Mediterranean diet, behavioral techniques and self-care strategies. Quality of life, perceived stress and disease activity were assessed with standardized questionnaires (IBDQ, SF-36, PSS, CAI). In addition, the distribution of circulating lymphocytes and lymphocyte subsets as well as the beta-adrenergic modulation of TNF-alpha production in vitro were analyzed. Urine catecholamines and plasma cortisol, prolactin and growth hormone were measured pre- and postinterventionally, and were compared with a healthy control group (n = 10). RESULTS: In response to therapy, patients in the intervention group showed significantly greater improvement in the SF-36 scale Mental Health and the Psychological Health Sum score compared with changes observed in the usual-care waiting control group. Patients in the intervention group showed significantly greater improvement on the IBDQ scale Bowel Symptoms compared with the control group. However, no significant group differences in circulating lymphocyte subsets or endocrine parameters were observed in response to therapy. In addition, no significant effects of intervention on either the basal levels of TNF-alpha or the suppressive action of the beta-adrenergic agonist isoproterenol on TNF-alpha production were observed. CONCLUSION: Mind-body therapy may improve quality of life in patients with UC in remission, while no effects of therapy on clinical or physiological parameters were found, which may at least in part be related to selective patient recruitment.

Adult↗
PubMed2005

Clinical and psychological correlates of quality-of-life in polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) has been shown to cause a reduction in quality of life. This study examines the extent of different PCOS symptoms on quality-of-life, psychosocial well-being and sexual satisfaction. METHODS: Complete metabolic, hormonal, clinical and psychosocial data were obtained from a total of 120 women with PCOS. Patients were compared with 50 healthy women to establish reductions in quality-of-life and emotional well-being. In addition, the correlation between psychosocial variables and the major clinical PCOS features obesity (body mass index (BMI)), excessive body hair (hirsutism score), acne, hyperandrogenism (serum testosterone levels), disturbed insulin regulation (area under the insulin response curve and homeostasis model assessment of insulin resistance), menstrual cycle disturbances and infertility were analyzed. RESULTS: PCOS patients showed significant reductions in quality-of-life, increased psychological disturbances, and decreased sexual satisfaction when compared with healthy controls. BMI and hirsutism scores, but not the presence of acne, were associated with physical aspects of quality-of-life and sexual satisfaction. No clear effect of androgens or insulin resistance on psychosocial variables was detected. Similarly, the type of menstrual cycle disturbances or infertility had no impact on psychological well-being. CONCLUSION: In PCOS, changes in appearance, particularly obesity and hirsutism, reduce physical dimensions of quality-of-life and decrease sexual satisfaction. The role of biochemical, endocrine and metabolic parameters as well as menstrual irregularities and infertility appeared to be less important. Clinicians should pay attention to the psychosocial dimensions of PCOS on an individual basis, regardless of symptom severity or treatment response.

Acne Vulgaris↗
PubMed2005

The dental anxiety scale and effects of dental fear on salivary cortisol.

Only a few studies have investigated use of the Dental Anxiety Scale in dental fear-induced neuroendocrine changes. The present study examined 19 female patients, each at two timepoints across an educational and a treatment session within periodontitis therapy. Subjective measures included a visual analogue scale, the STAI State scale, and the Dental Anxiety Scale. Salivary cortisol was measured in parallel across all four timepoints. Although patients were significantly more aroused and anxious prior to the treatment session, salivary cortisol remained unchanged. However, patients with high Dental Anxiety were significantly more aroused and anxious and showed significantly higher salivary cortisol during the educational session than those with low scores on Dental Anxiety. In conclusion, the Dental Anxiety Scale differentiated mean neuroendocrine change between patients scoring low and high for Dental Anxiety and its use as an accurate tool to identify patients with high dental anxiety should be further studied predictively.

Adolescent↗
PubMed2004

Repeated acupuncture treatment affects leukocyte circulation in healthy young male subjects: a randomized single-blind two-period crossover study.

Acupuncture is the most popular component of traditional Chinese medicine in western countries, which has been widely used in the treatment of numerous medical conditions, e.g., pain, emesis or asthma. However, the effects of acupuncture on neuroendocrine and immune functions in humans remain unclear. Therefore, the present study was performed to analyse whether acupuncture treatment affects leukocyte circulation as well as plasma levels of cortisol and norepinephrine in humans. Ten healthy young male subjects were enrolled in a randomized single-blind two-period crossover study. Each period contained three sessions of either acupuncture or sham acupuncture (placebo) treatment. After randomisation, the group 1 (n=5) received acupuncture treatment at acu-points ST36, LI11, SP10, and GV14, while sham acupuncture was performed for group 2 (n=5). Two weeks later, each group received the alternative treatment. Blood samples were taken before needling, 10 min after, and 30 min after removing the needles in the first and the third session. In addition, blood pressure and heart rate were determined simultaneously. Although acupuncture treatment did not affect leukocyte circulation in peripheral blood after the first session, we observed a significant decrease in leukocyte and lymphocyte values after the third session. In contrast, cortisol and norepinephrine plasma levels remained unchanged by acupuncture. These data indicate that repeated acupuncture treatment can affect leukocyte circulation in healthy humans by still unknown mechanisms.

Acupuncture Therapy↗
PubMed2004

In vitro adrenergic modulation of cellular immune functions in experimental autoimmune encephalomyelitis.

OBJECTIVE: To analyze the effects in vitro of alpha- and beta-adrenoceptor agonists on splenocyte proliferation and on proinflammatory cytokine production in splenocytes and peritoneal macrophages (MF) in different stages of EAE. METHODS: Splenocytes and peritoneal macrophages were harvested in the acute phase of EAE and in remission, and from controls. The beta-agonist terbutaline, the alpha(1)-agonist methoxamine, and the alpha(2)-agonist UK-14304 were added with ConA or lipopolysaccharide (LPS). TNF-alpha and IFN-gamma contents in supernatant and splenocyte proliferation were determined. RESULTS: Terbutaline and UK-14304 significantly suppressed TNF-alpha production by MF. However, EAE acute phase rats were resistant to the suppressive effect of UK-14304. Terbutaline significantly suppressed IFN-gamma and TNF-alpha production by splenocytes. EAE acute phase and remission animals showed reduced terbutaline-induced inhibition of IFN-gamma production. CONCLUSIONS: Disturbed sympathetic-immune communication in EAE is characterized by alterations in adrenergic sensitivity via both alpha- and beta-adrenergic pathways.

Adrenergic Agonists↗
PubMed2004

Neuroendocrine response to casino gambling in problem gamblers.

Problematic gambling is thought to be influenced by neurobiological mechanisms. However, the neuroendocrine response to gambling is largely unknown. Therefore, the effect of casino gambling on the sympathoadrenal system, the HPA-axis, and pituitary hormones were analyzed. Fourteen male problem gamblers and 15 non-problem gamblers were examined in a balanced cross-over design. In the experimental session, participants played blackjack in a casino wagering their own money. During the control session, subjects played cards for accumulation of points. Heart rate and endocrine measures were recorded at baseline, at 30, 60 and 90 min during gambling/card playing, and after the game. Heart rate and norepinephrine levels increased with the onset of blackjack in both groups, with problem gamblers showing significantly higher levels across the entire gambling session. In addition, dopamine levels were significantly higher in problem gamblers during casino gambling compared to non-problem gamblers. Cortisol levels were transiently increased with the onset of blackjack in both groups. Casino gambling as a "real life" situation induces activation of the HPA-axis and the sympathoadrenergic system, with significantly more pronounced changes in problem gamblers. These findings may contribute to a better understanding of neuroendocrine disturbances in problem gambling.

Adrenocorticotropic Hormone↗
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

Are there alterations of neuroendocrine and cellular immune responses to nutrients in women with irritable bowel syndrome?

OBJECTIVES: The goal was to investigate the neuroimmune axis in irritable bowel syndrome (IBS) by analyzing the neuroendocrine and cellular immune responses to nutrient load. METHODS: In the fasting state and 20, 40, 70, and 100 min following nutrient load, blood samples were collected and cardiovascular recordings were accomplished in 15 female IBS patients and 15 healthy women. Plasma norepinephrine, prolactin, cortisol, and growth hormone were analyzed, and blood pressure and heart rate responses were measured. The distribution of peripheral leukocytes and lymphocyte subpopulations and the in vitro production of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) after whole blood stimulation with in lipopolysaccharide (LPS) were analyzed. RESULTS: IBS patients demonstrated significantly greater postprandial increases in plasma norepinephrine and systolic blood pressure (p < 0.05), but no cortisol response. A postprandial redistribution of circulating leukocytes and lymphocyte subpopulations was observed in both groups, including significant increases in the numbers of leukocytes and granulocytes and significant decreases in the numbers of monocytes, T-cells, and natural killer (NK) cells (all p < 0.05). However, IBS patients demonstrated significantly greater postprandial increases in leukocytes and granulocytes, while changes in the numbers of monocytes and NK cells were significantly diminished (all p < 0.05). Patients also failed to show the postprandial decrease in the in vitro TNF-alpha production observed in controls. Postprandial norepinephrine concentrations were negatively correlated with NK cell numbers in IBS patients (r= 0.58, p < 0.05) but not controls. CONCLUSIONS: IBS may involve an autonomic hyper-responsiveness to visceral stimuli, which occurs throughout the entire gut, is independent of acutely perceived GI symptoms, and does not necessarily involve HPA axis activation. Women with IBS show altered cellular immune responses to food intake, which may at least in part be mediated by adrenergic mechanisms. Thus, autonomic disturbances may have implications for cellular immune function along the neuroendocrine-immune axis in patients with IBS.

Adult↗
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

Effects of sexual arousal on lymphocyte subset circulation and cytokine production in man.

OBJECTIVE: Sexual arousal and orgasm induce an increase in sympathetic activity as well as in catecholamine and prolactin plasma concentrations. However, the effects of sexual arousal and orgasm on immune functions in man are unknown. Thus, this study investigated the effects of masturbation-induced orgasm on lymphocyte circulation and cytokine production in healthy young males. METHODS: In a crossover design, 11 volunteers completed an experimental condition in which they were asked to masturbate until orgasm and to participate in a control condition without sexual activity. Blood was drawn continuously for determination of endocrine parameters. In addition, leukocyte and lymphocyte subsets were analyzed via flow cytometry, and the production of lipopolysaccharide-induced interleukin 6 and tumor necrosis factor alpha was measured before and then 5 and 45 min after the orgasm. RESULTS: The results confirmed transient increases in adrenaline and prolactin plasma concentrations. Sexual arousal and orgasm increased the absolute number of leukocytes, in particular natural killer cells (CD3-CD16+CD56+), in the peripheral blood. In contrast, T cell (CD3+) and B cell (CD3-CD20+) subpopulations as well as the production of interleukin 6 and tumor necrosins factor alpha remained unaffected by sexual activity. CONCLUSION: These findings demonstrate that components of the innate immune system are activated by sexual arousal and orgasm.

Adult↗
PubMed2003

G protein beta3 subunit 825T allele is associated with depression in young, healthy subjects.

This study investigated the relationship between the G protein beta3 subunit 825T allele and depression in young, healthy subjects. 825T and 825C allele carriers were characterized among 190 healthy medical students. State depression was assessed by the Becks Depression Inventory, supplemented by subscales of the Freiburg Personality Inventory, and Questionnaire for Measuring Factors of Aggression which assess trait depression. Depression of homo- and heterozygous 825T allele carriers was compared to 825C allele carriers via multi-level statistical analysis. 825T allele carriers displayed higher levels of depression, as measured by each questionnaire. Regression analysis demonstrated that allele type was the single predictor of depression. The predictive capacity of the 825T allele in depression was further supported by odds-ratio analysis. We conclude that the G protein beta3 subunit 825T allele is predictive of depressive mood in a young, healthy population.

Adult↗
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↗
PubMed2003

Central catecholamine depletion inhibits peripheral lymphocyte responsiveness in spleen and blood.

Experimental and clinical evidence has demonstrated extensive communication between the CNS and the immune system. To analyse the role of central catecholamines in modulating peripheral immune functions, we injected the neurotoxin 6-hydroxydopamine (6-OHDA) i.c.v. in rats. This treatment significantly reduced brain catecholamine content 2, 4 and 7 days after injection, and in the periphery splenic catecholamine levels were reduced 4 days after treatment. Central catecholamine depletion induced an inhibition of splenic and blood lymphocyte proliferation and splenic cytokine production and expression (interleukin-2 and interferon-gamma) 7 days after injection. In addition, central treatment with 6-OHDA reduced the percentage of spleen and peripheral blood natural killer (CD161 +) cells, and T-cytotoxic (CD8 +) cells in peripheral blood. The reduction in splenocyte proliferation was not associated with a glucocorticoid alteration but was completely abolished by prior peripheral sympathectomy. These data demonstrate a crucial role of central and peripheral catecholamines in modulating immune function.

Animals↗
PubMed2003

Acute neuroendocrine response to sexual stimulation in sexual offenders.

BACKGROUND: Several pharmacotherapeutic approaches have confirmed the influence of neuroendocrine parameters on sexual desire, function, and fantasies in men; however, the relevance of acute neuroendocrine changes in mediating heightened sexual drive remains unknown. We recently demonstrated that plasma prolactin substantially increases following orgasm in healthy men, suggesting a feedback mechanism for peripheral prolactin in the control of acute sexual arousal. Because prolactin appears to play a regulatory role in acute sexual drive, we initiated this study to see whether sexual offenders with a high sexual drive have a different neuroendocrine response to sexual arousal. This study compares the prolactin response to orgasm of sexual offenders with high sexual drive and that of healthy subjects with average sexual drive. METHODS: From a subject pool of 150 inpatients held because of sexual crimes, we recruited 10 volunteers, based on their high sexual drive according to an intensive, semistructured clinical interview. We defined sexual drive by a short refractory period and strong sexualization, or a high frequency of sexual stimulation. We analyzed the acute psychoneuroendocrine response to sexual arousal and orgasm continuously before, during, and after masturbation-induced orgasm in patients and control subjects. RESULTS: Sexual offenders demonstrated higher sexual desire (P < 0.001) and function (P < 0.001) and a more positively perceived refractory period (P < 0.05). Both groups displayed a prolonged, significant increase in prolactin plasma levels after orgasm (P < 0.001). Sexual offenders did not differ from control subjects in neuroendocrine response to sexual arousal and orgasm. CONCLUSIONS: These data demonstrate that sexual offenders with a high sexual drive do not differ from control subjects in the postorgasmic neuroendocrine response, particularly in prolactin release. This study confirms that factors other than peripheral hormones influence deviant sexual behaviour.

Adult↗