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Results for “Neuroimmunomodulation”

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At least 307 records · Page 17Linked to original sources
PubMed2000

Immunotoxic effects of inorganic lead on host resistance of mice with different circling behavior preferences.

We have observed differential immune responses in mice with different circling preferences, which are posited to reflect interindividual immune response differences influenced by brain laterality effects on neuroimmune circuits. In this study, we have investigated the influence of inorganic lead (Pb) and/or Listeria monocytogenes (LM) infection on the cytokine and corticosterone (CORT) levels of mice grouped by lateralized behavior. Pb increased the LM susceptibility of mice with both left (LC)- and right-circling (RC) preferences; however, Pb did not inhibit the host resistance of mice with no circling preference (NP mice). The basal serum IFNgamma levels were lowered in all groups after Pb exposure, which coincided with a decrease in host resistance in LC and RC mice, but not NP mice. Pb also altered the basal serum CORT levels, and these changes appear to correlate better with changes in the host resistance of all groups. The basal CORT levels were significantly lowered by Pb in mice with a circling preference, and Pb significantly suppressed the host resistance of mice with a circling preference. However, Pb slightly increased the serum CORT level of NP mice, and their host resistance was slightly improved by Pb. After infection, the increase in CORT levels was associated with an increase in the serum IL-6 levels, which may reflect cytokine influences on the hypothalamic-pituitary-adrenal axis. At 3 days after infection, the serum IL-6 level seems to be a good indicator of the severity of the infection. We suggest that environmental stressors can reorder the observed differential susceptibility to LM in mice with different circling preferences, in that relatively resistant mice (RC mice) become more susceptible than NP mice after exposure to Pb. The results suggest that environmental stressors may have differential effects among individuals with endogenous differences in their neuroimmune circuits, since brain laterality is known to influence immune functions.

Animals↗
PubMed2001

Cytokine-induced sickness behavior: where do we stand?

Sickness behavior refers to the coordinated set of behavioral changes that develop in sick individuals during the course of an infection. At the molecular level, these changes are due to the effects of proinflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNFalpha), in the brain. Peripherally released cytokines act on the brain via a fast transmission pathway involving primary afferent nerves innervating the body site of inflammation and a slow transmission pathway involving cytokines originating from the choroid plexus and circumventricular organs and diffusing into the brain parenchyma by volume transmission. At the behavioral level, sickness behavior appears to be the expression of a central motivational state that reorganizes the organism's priorities to cope with infectious pathogens. There is clinical and experimental evidence that activation of the brain cytokine system is associated with depression, although the exact relationship between sickness behavior and depression is still elusive.

Brain↗
PubMed2002

Mechanism of norepinephrine-mediated inhibition of human NK cytotoxic functions: inhibition of cytokine secretion, target binding, and programming for cytotoxicity.

Norepinephrine (NE) has been shown to inhibit human peripheral blood-derived natural-killer (NK) cell cytotoxicity (NKCC) in vitro. We demonstrate in this study that NE not only inhibits IL-2-activated NKCC but antibody-dependent cellular cytotoxicity (ADCC) as well. NK cytotoxicity by purified NK cells against K562 (NKCC) and against Raji cells (ADCC) were inhibited by NE (1-100 microM) by more than 50% in a 4-h (51)Cr release assay. The mechanism underlying the inhibition has been examined. NK cytotoxicity is dependent on target recognition and formation of NK-target conjugates, and activation by IL-2 is dependent on the secretion of cytokines (such as TNF-alpha) by NK cells. We hypothesized that the inhibition of NK functions by NE may be due to disruption of NK-target conjugation, blocking programming for lysis, and/or inhibition of cytokine secretion. Pretreatment of human peripheral blood mononuclear cells (PBMC) with NE for 15 min significantly reduced the binding to K562 cells by CD16(+) NK lymphocytes. In the presence of K562 cells, NE down-regulated the expression of CD16 (FcgammaRIII) by human PBMC, an NK cell receptor responsible and necessary for ADCC and cytokine secretion. We also demonstrate that NE inhibited the IL-2-mediated up-regulation of the activation marker CD69. At concentrations of 10(-6) to 10(-5) M, NE inhibited TNF-alpha, IFN-gamma, and GM-CSF secretion by NK cells, which are essential for IL-2-driven NK maturation and functions. In addition, using single-cell analysis, NE pretreatment of lymphocytes reduced the frequency of killer cells in the NK-K562 conjugate population in a concentration-dependent manner, indicating an inhibition of the programming for lysis by NK cells. In summary, these data demonstrate that NE-induced inhibition of NK cytotoxicity is manifested at multiple levels, including a modification of NK cell receptor ligation to target cells, blockade of NK cytokine secretion necessary for NK maturation and differentiation, and inhibition of the target-induced activation of the cytotoxic mechanism(s) in NK cells. Thus, sympathetic activation, as often induced experimentally, may profoundly impair natural cellular immunity through varied measurable pathways.

Antigens, CD↗
PubMed2002

Cyclic estradiol treatment enhances the effects of interleukin-1beta on food intake in female rats.

Proinflammatory cytokines elicit behavioral and physiological responses that include decreased food intake, fever, and a general disinterest in usual activities. Ovarian hormones modulate immune system activity and responsiveness to cytokines in female mammals, suggesting that sex differences in immune function may be influenced by gonadal steroids. In this experiment, female adult rats were ovariectomized and given two daily subcutaneous injections of 5.0 or 20.0 microg of estradiol benzoate or the oil vehicle 3 weeks after surgery. Following 2 days of hormone treatment, animals received ip injections of interleukin-1beta (IL-1beta) or saline 1 h before light offset. Food and water intake was measured 2 h after light offset. The results indicate that a cyclic pattern of estradiol treatment enhances the anorectic effect of IL-1beta and suggest that responses to immune system activation are influenced by estradiol.

Animals↗
PubMed2002

Age-related changes in noradrenergic sympathetic innervation of the rat spleen is strain dependent.

Previous findings from our laboratory revealed an age-related decline in noradrenergic (NA) sympathetic innervation of the spleen in male Fischer 344 (F344) rats. The purpose of this study was to determine whether other rat strains also progressively lose NA sympathetic nerves in the aging spleen. Sympathetic innervation of spleens from 3- and 21-month-old male F344, Brown Norway (BN), BN X F344 (BNF(1)), and Lewis rats was examined using fluorescence histochemistry to localize catecholamines combined with morphometric analysis and using high-performance liquid chromatography with electrochemical detection for measuring norepinephrine (NE). Neurochemistry revealed a significant age-related decline in NE concentrations in spleens from F344 and Lewis rats. In contrast, there was no effect of age on splenic NE concentrations in BN or BNF(1) rats. Consistent with neurochemical analysis, fluorescence histochemistry revealed a striking decline in NA innervation of spleens from old F344 and Lewis rats not observed in the other two strains. However, in BN and BNF(1) rats, nerve fibers were diminished in distal portions of the spleen but not in the hilar regions. Morphometric analysis confirmed neurochemical and histological findings, revealing approximately 65-70% loss in NA nerve density in spleens from F344 and Lewis rats. These findings indicate that age-related changes in sympathetic innervation of the rat spleen are strain-dependent. Whether the loss of sympathetic nerves in spleens from F344 and Lewis rats is associated with age-related changes in the splenic microenvironment remains to be determined. The functional significance of altered sympathetic innervation of the spleen with advancing age is discussed.

Aging↗
PubMed2002

Endocrine and cytokine responses to acute psychological stress in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system. An impaired hypothalamopituitary axis and stress reactivity have extensively been discussed without convincing experimental evidence. We choose a standardized acute psychological stressor to determine whether MS patients show altered endocrine and immune responses to stress. In 35 relapsing-remitting MS patients we found elevated baseline levels for catecholamines, prolactin, and IL-6 compared to 15 healthy controls. All neuroendocrine parameters declined during the stress intervention in MS as well as in stress-exposed controls. But only prolactin showed a significantly larger decline in stressed MS patients versus controls. During exposure to the stress we found no significant changes in serum levels of IL-6, IL-6 receptor, or TNF-alpha in either MS patients or controls after stimulation of a whole blood culture. An altered neural immune signaling in relapsing-remitting MS patients during acute experimental stress could not be proven for the parameters analyzed.

Acute Disease↗
PubMed2002

Temporal stability of acute stress-induced changes in leukocyte subsets and cellular adhesion molecules in older adults.

This study investigated the temporal stability of enumerative immune and catecholamine responses to acute psychosocial stress in 67 Alzheimer's caregivers ages 56-82 years (45 women and 22 men) who were required to prepare and deliver two 3-min speeches on three occasions at 2-week and 6-week intervals. All leukocyte subsets and adhesion molecules (CD62L and CD11a) changed significantly from rest to postspeak at each of the three testing sessions (p's <.0005). Responses showed moderate to high temporal stability across baseline and absolute task values (r's =.65-.96). Reliability was predictably lower for both forms of change scores (r's = -.16-.64). The level of temporal stability achieved is comparable to that seen previously in younger adults, indicating that acute psychosocial stress produces reliable changes in circulating leukocytes and cell adhesion molecules in older adults.

Aged↗
PubMed2002

Changes in the leukocyte distribution and surface expression of adhesion molecules induced by hypothalamic stimulation in the cat.

Emotions and the neuroendocrine system are known to affect leukocyte distribution. However, there have so far been few reports on the relationship between hypothalamically induced emotional behavior and the endocrine-immune response. We previously reported changes in the leukocyte distribution and adhesion molecules induced by anteromedial hypothalamus stimulation (AH stimulation), which elicits restlessness behaviors in the cat. In this study, we examined ventromedial hypothalamus stimulation (VMH stimulation), which elicits threat behaviors. In addition, the endocrine responses after VMH stimulation were evaluated. VMH stimulation as well as AH stimulation induced elevations of plasma cortisol and epinephrine levels and granulocytosis and lymphopenia. In contrast, VMH stimulation induced only an elevation of plasma norepinephrine and elicited an opposite pattern of CD62L expression on the leukocyte subpopulations. The different endocrine-immunological reactions between VMH stimulation and AH stimulation were thus associated with different types of behavioral responses.

Animals↗
PubMed2002

Phenylethanolamine N-methyl transferase expression in mouse thymus and spleen.

Catecholamines usually are found in neurons and chromaffin cells of mammals. In this study, surprisingly high levels of the epinephrine synthesizing enzyme phenylethanolamine N-methyl transferase (PNMT) were detected in the thymus of young mice. Levels of PNMT activity in the thymus were comparable to levels in the brainstem and were suppressed by the PNMT inhibitor LY134046. PNMT mRNA was localized with in situ hybridization throughout the thymus, but levels were approximately twofold higher in the cortex than in the medulla. PNMT activity was barely detectable in the spleen, and only a few cells expressing PNMT mRNA were located in the marginal zone of the white pulp. These findings suggest that cells in the thymus of young mice have the ability to synthesize epinephrine.

Age Factors↗
PubMed2002

Norepinephrine, the beta-adrenergic receptor, and immunity.

Over the past 20 years, a significant effort has been made to define a role for the neuroendocrine system in the regulation of immunity. It was expected that these experimental findings would help to establish a strategy for the development of clinical interventions to either suppress or augment immunological function for disease prevention. However, the translation of these basic experimental findings into clinical interventions has been difficult. Possible explanations for this difficulty are that the findings from human and animal studies do not agree and/or that the results obtained within one species are rarely verified in the other. Our goal in writing this review is to address this issue by summarizing the published findings from human studies and comparing them to published findings from animal studies. Although far from being exhaustive, this review summarizes and discusses at least the past 10 years of findings in which a change in immunity and a change in catecholamine levels and/or stimulation of the beta(2)-adrenergic receptor has been documented.

Humans↗
PubMed2001

In vitro cytokine secretion in individuals with schizophrenia: results, confounding factors, and implications for further research.

The present paper reviews the results of all publications on in vitro cytokine secretion in patients with schizophrenia, as published by March 2001. The authors supply easy to read tables with respect to the individual cytokines and soluble cytokine receptors investigated, the in vitro methodology used, characterization of the patient samples, and the results on cytokine secretion as stated in these studies. Inconsistent results, e.g., regarding in vitro secretion of IL-2 with 11/18 studies finding decreased secretion, 5/18 finding no change, and 2/18 finding increases, cannot systematically be correlated with any methodological procedures nor any diagnostic subtypes, per se. However, factors such as medication and cigarette smoking are likely to play a role. The authors suggest that more hypothesis-driven research, together with more carefully designed studies, as well as better communication between basic or animal researchers and clinicians might help to answer the question of whether there are meaningful peripheral changes in the immune system related to schizophrenia.

Antipsychotic Agents↗
PubMed2001

T-helper-1 and T-helper-2 responses in psychiatric disorders.

The expanding field of psychoneuroimmunology has markedly increased knowledge about the interference of the central nervous system and the immune system. Immunological abnormalities in psychiatric patients have been repeatedly described in the last century. Modern concepts of immunology and the growing knowledge of psychoneuroimmunology may help in understanding the distinct immunological mechanisms in psychiatric disorders. One of these concepts regarding the adaptive immune system is the discrimination between Th1-like cell-mediated and Th2-like antibody-related immune responses. This article systematically describes alterations of Th1- or Th2-specific parameters in the major psychiatric disorders schizophrenia, major depression, and Alzheimer's disease. There are several hints of associations of these two distinct arms of immune response with subgroups of schizophrenia and major depression. The immunological research in Alzheimer's disease has already led to a preclinical model of immunotherapy. Categorization of immune parameters may also help to identify a possible immune-related pathophysiology in psychotic and affective disorders, resulting in specific treatment strategies.

Humans↗
PubMed2001

Review of immunological and immunopathological findings in schizophrenia.

The involvement of immunological and immunopathological mechanisms in the etiopathogenesis of schizophrenia has been a matter of research, with recently increasing effort. This article reviews the findings focusing on postmortem neuropathology, the blood-brain barrier, antibodies, acute phase proteins, immunocompetent cells, and activation markers of immunocompetent cells. Evidence for the two primarily postulated hypotheses (the infectious hypothesis and the autoimmune hypothesis) is critically discussed. On the basis of the findings, perspectives for future research are outlined aiming at a precise and consequent strategy to elucidate a potential involvement of immune mechanisms in the etiopathogenesis of schizophrenia.

Humans↗
PubMed1996

The dendritic cell: its potent role in the respiratory immune response.

The importance of the dendritic cell for the capture of antigens and initiating an immune response is now well recognized. Whereas much is known about their structure and function, their lineage is still not clear. Studies in vitro have demonstrated that the regulated maturation of function that occurs in culture explains many of the in vivo events relating to antigen capture and presentation. The control over maturation and migration of these cells to the immune system is decisive as to whether an immune response is mounted or not. 'Danger' signals provided by conserved bacterial products or by microenvironmental cytokines are important regulators. Dendritic cells have been clearly involved in the development of respiratory disease and our understanding of their involvement will have an impact on our future therapeutic strategies.

Animals↗
PubMed1996

Effect of melatonin on NF-kappa-B DNA-binding activity in the rat spleen.

It was recently demonstrated that the pineal neurohormone melatonin is a hydroxyl radical scavenger and antioxidant, and that it plays an important role in the immune system. In studies reported herein, we have investigated the relationship of the melatonin level and the NF-kB DNA binding activity in the spleen of Sprague. Dawley rats. These in vivo results indicate that NF-kB DNA binding activity in the spleen is lower at night, when endogenous melatonin levels are elevated, than during the day, when endogenous melatonin levels are lower. Furthermore, exogenously administered melatonin (10 mg/kg) was shown to cause a significant decrease in NF-kB DNA binding activity in the spleen at 60 min after intraperitoneal injection (as compared with vehicle-treated rats). These new findings suggest that the normal night time rise which can be expected for melatonin may be associated with increased NF-kB DNA binding activity in the spleen. The melatonin, therefore, could potentially act to modulate spleen function and/or the immune system by regulating the NF-kB DNA binding activity in the spleen.

Animals↗
PubMed1999

Mechanisms underlying immunologic states during pregnancy: possible association of the sympathetic nervous system.

NK and extrathymic T cells are abundant in the decidua of the pregnant uterus. To determine how this unique pattern is induced, overall populations of leukocytes were examined in the blood and other tissues in pregnant women. Time-kinetic studies showed that a basal change of leukocytes during pregnancy was granulocytosis and lymphocytopenia in the blood. This change might be due to sympathetic nerve activation during pregnancy, because the administration of catecholamine is known to activate myelopoiesis in the bone marrow. In addition to the numerical change, the functional activation of NK and extrathymic T cells also seemed to be present. This might be due to NK cells and extrathymic T cells (as well as granulocytes), which carry a high density of surface adrenergic receptors. Such functional activation of NK and extrathymic T cells was more prominent in the blood and urine in patients with preeclampsia and hyperemesis gravidarum than in normal pregnant women. The present results suggest that the activation of granulocytes, NK cells, and extrathymic T cells is essential for the maintenance of pregnancy but that overactivation thereof may be responsible for the onset of pregnancy disorders.

Adult↗
PubMed2001

Rapid and transient reduction in circulating thyroid hormones following systemic antigen priming: implications for functional collaboration between dendritic cells and thyroid.

The thyroid hormones T(3) (tri-iodothyronine) and T(4) (thyroxine) are disseminated throughout the body via the circulation and are maintained across a range of physiological concentrations under the control of thyroid-stimulating hormone (TSH). T(3) (and T(4) after conversion to T(3)) influences many biological activities, including gene expression and protein synthesis, though little is known about the nature of pituitary-thyroid immune interactions. In the present study we show that serum T(3) and T(4) levels are sharply but transiently reduced during the first 24 h of systemic antigen exposure and that this is followed by suppressed levels of free T(4), after which there is rapid recovery to normal levels. Splenic dendritic cells, depending upon the stage of maturation/activation, were found to be a rich source of TSH, and CD11c(+) cells with dendritic cell morphology were present in the thyroid 1-3 days after antigen exposure. Moreover, antigen priming of hypophysectomized mice that are unable to make pituitary-derived TSH resulted in significant increases in circulating T(4), implying that compensation in the drop in thyroid hormones can be regulated from extrapituitary sources. These findings thus identify a novel set of immune-endocrine interactions that transpire during the early phase of antigen exposure, and they suggest that under appropriate conditions the immune system directly participates in the process of maintaining physiological homeostasis by contributing to the regulatory control of thyroid hormone activity.

Animals↗