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Neurotransmitters and cytokines in CNS pathology.

In summary, we have demonstrated an in vitro model for oligodendrocyte cell death that may be relevant to events in formation of lesions in MS. It involves cell contact to oligodendrocytes with activated, viable microglia (or inflammatory macrophages), surface TNF-alpha, surface adhesion molecules, and production of NO. Precise mechanisms of TNF-alpha and ICAM-1/LFA-1 participation and the nature of the susceptibility of the oligodendrocyte are currently being studied.

AIDS Dementia Complex↗

Immune promotion of central nervous system remyelination.

Remyelination by oligodendrocytes is the normal response to injury of the central nervous system following experimental demyelination by toxins and viruses in rodents. By contrast, in immune-mediated myelin disorders such as human MS, Theiler's virus-induced demyelination or EAE, remyelination is incomplete. We have considered two hypotheses to explain why myelin repair is incomplete in these disorders. Hypothesis I is that myelin repair is the normal consequence of primary myelin injury but there are immune factors which prevent its full expression. To test hypothesis I, we depleted T cells in Theiler's virus infected mice with cyclophosphamide or with monoclonal antibodies to CD4, CD8, or immune response gene products (Ia). Enhanced remyelination and proliferation of glial cells was observed in mice depleted of CD4+ or CD8+ T cells. Hypothesis II is that there are immune factors within some demyelinated lesions which, when present, promote new myelin synthesis. We envision these factors to be present in those lesions showing remyelination but absent in those lesions that remain demyelinated. To test hypothesis II, we generated polyclonal immunoglobulins directed against normal CNS antigens. Transfer of immunoglobulins from mice immunized repeatedly with spinal cord homogenate resulted in 4-5-fold enhancement of remyelination in Theiler's virus infected mice. We have also generated a series of monoclonal antibodies directed against normal autoantigens which also promote CNS remyelination. These experiments support the concept that full CNS remyelination is possible in human demyelinating diseases such as MS. Manipulation of the immune response either by inhibiting the function of T cells or by treatment with immunoglobulins (possibly normal autoantibodies) appears to promote remyelination. These experiments provide hope for patients with fixed neurological deficits for whom there are currently no available therapies.

Adjuvants, Immunologic↗

Mind-body medicine in primary care. Implications and applications.

A growing body of research in basic and clinical science confirms that psychological states and interventions affect physiologic and pathophysiologic processes and the outcome of clinical illness. This evidence is reviewed in detail, with special attention paid to those findings that have particular relevance for primary care physicians. Specific guidelines are offered for incorporating mind-body principles and techniques into primary care practice.

Animals↗

The disodium salt of EDTA inhibits the binding of vasoactive intestinal peptide to macrophage membranes: endodontic implications.

The purpose of this study was to investigate the effect of the disodium salt of ethylenediamine tetraacetate (EDTA), a calcium ion chelator used in the root canal therapy, on vasoactive intestinal peptide (VIP) binding to macrophage membranes (MM's). Binding assays were conducted at 15 degrees C in 0.5 ml of 50 mM Tris-HCl buffer (pH 7.5) containing 1.6% (w/v) bovine serum albumin, 1.2 mg/ml of bacitracin, and different EDTA concentrations, using 45 pM of [125I]VIP as tracer. Results showed that EDTA inhibits VIP binding to MM's in a dose-dependent manner, with an IC50 value of 5.4 mM (p < 0.01). EDTA concentrations equal or higher than 100 mM of abolished VIP-MM interaction. Taking into account that the macrophage plays an essential role in inflammatory reactions and the immune response, we conclude that the apical extrusion of EDTA during root canal therapy could modify VIP-macrophage interaction modulating the inflammatory mechanisms involved in periapical lesions.

Animals↗

Immunohistochemical study of gamma-aminobutyric acid and bombesin/gastrin releasing peptide in human dental pulp.

This study investigated the presence of the putative peripheral neuromodulators Gamma-aminobutyric Acid (GABA) and Bombesin/Gastrin-Releasing Peptide (BN/GRP) in the human tooth pulp. Caries free and asymptomatic carious teeth were processed for paraffin embedding and sectioned at six microns. From each specimen, sections were stained with hematoxylin and eosin; other sections were subjected to Avidin-Biotin-Peroxidase Complex immunohistochemistry for GABA and BN/GRP. Sections of rat brain and small cell lung carcinoma served as positive controls. Results indicate the presence of specific GABA-like and BN/GRP-like immunoreactivity within the pulps of both normal and carious teeth. Overall staining for both ligands was significantly more intense within inflamed pulps. Based on their actions elsewhere, GABA and BN/GRP may play a role in the dental pulp as peripheral neuromodulators or as growth factors.

Animals↗

Ontogeny of IgA(+) cells in lamina propria: effects of sympathectomy.

The effect of chemical sympathectomy on the ontogeny of the IgA(+) cells in the intestinal LP was examined in weanling rats. Ablation of the peripheral sympathetic nerve terminals using 6-hydroxydopamine (6-OHDA) on days 14 and 17 was associated with an increase in the number of IgA(+) and IgM(+) cells in the intestinal LP at 28, 30 and 35 days of age. Despite the precocious development of Ig-containing cells in the gut, the specific intestinal immune response to ovalbumin (OVA), induced by IP priming with OVA at 30 days of age and boosting ID 14 days later, was not altered by 6-OHDA treatment, with no difference observed in the numbers of total AOCC or IgA(+)/AOCC in the LP of treated, compared to control animals. The results presented in this study suggest that sympathetic innervation is an influential factor in the ontogeny of IgA(+) cells populating the intestinal lamina propria, although no functional significance in terms of the specific local response to a new antigen was detected using the immunisation model described here.

Animals↗

Immunoregulators in the nervous system.

The nervous system, through the production of neuroregulators (neurotransmitters, neuromodulators and neuropeptides) can regulate specific immune system functions, while the immune system, through the production of immunoregulators (immunomodulators and immunopeptides) can regulate specific nervous system functions. This indicates a reciprocal communication between the nervous and immune systems. The presence of immunoregulators in the brain and cerebrospinal fluid is the result of local synthesis--by intrinsic and blood-derived macrophages, activated T-lymphocytes that cross the blood-brain barrier, endothelial cells of the cerebrovasculature, microglia, astrocytes, and neuronal components--and/or uptake from the peripheral blood through the blood-brain barrier (in specific cases) and circumventricular organs. Acute and chronic pathological processes (infection, inflammation, immunological reactions, malignancy, necrosis) stimulate the synthesis and release of immunoregulators in various cell systems. These immunoregulators have pivotal roles in the coordination of the host defense mechanisms and repair, and induce a series of immunological, endocrinological, metabolical and neurological responses. This review summarizes studies concerning immunoregulators--such as interleukins, tumor necrosis factor, interferons, transforming growth factors, thymic peptides, tuftsin, platelet activating factor, neuro-immunoregulators--in the nervous system. It also describes the monitoring of immunoregulators by the central nervous system (CNS) as part of the regulatory factors that induce neurological manifestations (e.g., fever, somnolence, appetite suppression, neuroendocrine alterations) frequently accompanying acute and chronic pathological processes.

Adjuvants, Immunologic↗

Biological basis of the behavior of sick animals.

The most commonly recognized behavioral patterns of animals and people at the onset of febrile infectious diseases are lethargy, depression, anorexia, and reduction in grooming. Findings from recent lines of research are reviewed to formulate the perspective that the behavior of sick animals and people is not a maladaptive response or the effect of debilitation, but rather an organized, evolved behavioral strategy to facilitate the role of fever in combating viral and bacterial infections. The sick individual is viewed as being at a life or death juncture and its behavior is an all-out effort to overcome the disease.

Animal Diseases↗

Modulation of immune cell function by the autonomic nervous system.

This review discusses some of the major findings implicating the autonomic nervous system in the regulation of immune function. The sympathetic nervous system, the primary focus of this line of research, directly innervates the major lymphoid organs, and physiological release of sympathetic neurohormones at these sites has been documented. Leukocytes have been shown to express receptors for catecholamines, as well as neuropeptide Y, and studies in vitro and in vivo have indicated that occupation of these receptors by the appropriate ligands produces functional changes in immunological cells. Finally, altered sympathetic regulation may underlie some of the immunological abnormalities observed in chronic stress, clinical depression, and ageing.

Animals↗

Invertebrate molecular neuroimmune processes.

During the course of evolution, invertebrates and vertebrates have kept in common similar signaling molecules e.g. neuropeptides, opiates etc... Complete hormonal-enzymatic systems such as the opioid-opiate-cannabinoid systems have been found in both nervous central and immune systems of these animals. These signaling molecules can be found free in blood circulation and act as immunomodulators. The present review is focused on peptides derived from the opioid proopiomelanocortin precursor, the opiates and the endocannabinoids, which are very powerful immunosuppressors, and example models of the bidirectional communications between the endocrine and the immune systems. Parasites use these immunosuppressors with magnificence in their crosstalk with their host.

Animals↗

Influence of psychological stress on immune-inflammatory variables in normal humans. Part II. Altered serum concentrations of natural anti-inflammatory agents and soluble membrane antigens of monocytes and T lymphocytes.

The effects of academic examination stress on serum concentrations of interleukin (IL)-1 receptor (R) antagonist (A), soluble(s) IL-2R, sIL-6R, soluble glycoprotein 130 (sgp130), Clara cell protein (CC16), sCD8 and sCD14 were evaluated in 38 university students. The relationships among changes in the above immune-inflammatory variables, levels of serum cortisol, and scores on the Perceived Stress Scale (PSS) or the State-Trait Anxiety Inventory (STAI) were examined. Academic examination stress was associated with significant increases in PSS and STAI scores, and in serum sgp130 and sCD8 values. Academic examination stress was associated with significantly decreased serum sCD14 concentrations in students with high, but not low, stress perception. There were stress-induced differences in serum IL-1RA, sIL-6R and CC16 concentrations between students with high vs. low stress-induced anxiety. The stress-induced increase in serum sCD8 was significantly more pronounced in male students, whereas the increase in serum sgp130 was more pronounced in female students taking contraceptive drugs. These results suggest that: (1) psychological stress induces immune-inflammatory changes pointing toward complex regulatory responses in IL-6 signalling, a decreased anti-inflammatory capacity of the serum, and interactions with T cell and monocytic activation; and that (2) sex hormones may modify stress-induced immune-inflammatory responses.

Adaptation, Psychological↗

Bulimia nervosa and autoimmunity.

The autoantibodies that react with dopamine and serotonin are of interest in the study of bulimia nervosa. These neurotransmitters play an important role in appetite control, sexual and social behavior, and stress responses, all of which form a part of the clinical picture of bulimia nervosa. Are these autoantibodies involved in the serotoninergic hypofunctioning present in bulimia nervosa? Are they a part of an immunity regulation system essential for the cerebral system's homeostasis? To address these questions, 31 bulimic females (diagnosed according to DSM-III-R criteria) were compared with 10 control subjects (matched to the patients for sex, age, and demographic/psychosocial features). Measurement of the activity of natural autoantibodies reacting with dopamine, dopamine-beta-hydroxylase and serotonin was performed by an enzyme-linked immunosorbent assay (ELISA) for typical immunoglobulins (IgG, IgM, IgA). All of the autoantibodies of the IgG type were lower in the bulimic group than in the control group, a difference that was statistically significant for IgG anti-serotonin and IgG anti-dopamine. There was a trend for the amount of IgM anti-dopamine to be lower in patients than in controls. Dopamine and serotonin are specific components of brain cells. It can therefore be hypothesized that these antigens acting with autoantibodies could be the antigenic cerebral targets reacting with 'anti-brain' antibodies. The study of these specific autoantibodies provides information about the immunological characteristics that may be related to brain disturbances.

Adult↗

Stimulation of macrophage phagocytosis and lymphocyte count by exogenous prolactin administration in silver sea bream (Sparus sarba) adapted to hyper- and hypo-osmotic salinities.

Juvenile silver sea bream (Sparus sarba) were adapted to hyper- (33 ppt) and hypo-osmotic (6 ppt) salinities for 3 weeks and injected daily with ovine prolactin (1 microg/g body weight i.p.) during the last 7 days of the adaptation period. Fish injected with prolactin exhibited significant increases in percent phagocytosis and phagocytic index of both pronephric and splenic macrophages regardless of salinity. Prolactin injection also resulted in elevated blood lymphocyte counts in both hyper- and hypo-osmotically adapted sea bream. The present results provide further evidence for the existence of a neuroendocrine-immune link in teleosts.

Adaptation, Physiological↗